Learn more about hematopoietic stem cell differentiation and common markers used to phenotype both progenitors and terminally differentiated cells in the tabs below.

Maintenance of the mammalian blood system is dependent on hematopoietic stem cells (HSCs). HSCs are long-living multipotent stem cells with the potential to differentiate into all blood cell lineages. In mammals, hematopoiesis takes place in different sites during embryogenesis. These sites include the yolk sac, aorta-gonad mesonephros (AGM), and fetal liver. In adults, the differentiation of blood cells takes place primarily in bone marrow.

 

The classical model of hematopoiesis is viewed as a tree in which HSCs sequentially branch out into lineage-restricted progenitors of erythroid, myeloid, lymphoid, and megakaryocytic lineages. In this model, each progenitor is believed to represent a homogeneous population of cells with the equal potential to give rise to multiple lineages simultaneously.

 

However, despite evidence for hierarchical hematopoietic differentiation, recent studies have provided evidence suggesting there is clonal heterogeneity of multipotent and oligopotent progenitors. For example, it has been shown that on a population level, mouse CMPs are able to produce cells of myeloid, erythroid, and megakaryocytic lineages. Single-cell differentiation analysis of CMPs suggest that each clone is programmed to give rise to one type of blood cell only (i.e., macrophage, neutrophil, erythrocyte, megakaryocyte, etc.) Similar studies have also been done on other mouse and human progenitors including LMPP and GMPs.

Select a species to begin:
 
 

 

LT-HSC (Long-Term Hematopoietic Stem Cell)

LT-HSCs are pluripotent cells which give rise to all blood cell populations of lymphoid, myeloid, and erythroid lineages and  persist throughout the entire life-span. They have the potential to self-renew sustaining the stem cell pool or differentiate into ST-HSCs and other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells.

 

Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34-

CD135 (Flt3)-

CD150 (SLAM)+

ST-HSC (Short-Term Hematopoietic Stem Cell)

ST-HSCs are multipotent progenitors with a short-term renewal potential as compared to LT-HSCs. It is believed that ST-HSCs differentiate from the daughter cell during an asymmetrical division of LT-HSCs. ST-HSCs can give rise to other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells of lymphoid, myeloid and erythroid lineages.

 

Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)-

CD150 (SLAM)-

MPP (Multipotent Progenitor)

MPPs are multipotent progenitors derived from ST-HSCs. They can give rise to another multipotent progenitor, LMPPs, or oligopotent and unipotent progenitors which give rise to terminally differentiated cells.

 

Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)low

CD150 (SLAM)-

LMPP (Lymphoid-Primed Multipotent Progenitor)

LMPPs are responsible for the generation of lymphocytes and pDCs through subsequent differentiation steps including CLPs and pre-pDCs respectively. LMPPs were originally thought to be a homogeneous population of precursors containing multipotent cells with the equal potential to differentiate into several lymphoid lineages. However, a recent study has demonstrated that LMPP is a heterogeneous population of cells comprising unipotent clones with a non-overlapping lineage differentiation potential (21).

 

Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)hi

CD150 (SLAM)-

CD127 (IL-7Rα)-

CMP (Common Myeloid Progenitor)

CMPs are oligopotent progenitor derived from MPPs. This progenitor can differentiate into erythroid and myeloid lineages. It was originally believed that CMPs were a homogeneous population of precursor cells containing multipotent cells with the equal potential to differentiate into both myeloid and lymphoid lineages. However, a recent study has demonstrated that instead CMPs are a heterogeneous population of cells comprised of unipotent clones with a non-overlapping potential to give rise to an erythroid or myeloid lineage of cells (11,12).

 

Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34+

CD135 (Flt3)+/-

CD150 (SLAM)+/-

CD105 (Endoglin)-

CD16/32low

GMP (Granulocyte-Monocyte Progenitor)

GMPs are oligopotent progenitor derived from CMPs. This progenitor gives rise to monocytes, macrophages, granulocytes (neutrophils, basophils, and eosinophils), and some tissue dendritic cells through differentiation steps including GPs and cMOPs. A recent study suggests that GMPs are a heterogeneous population of cells comprised of unipotent clones with a nonoverlapping potential to give rise to monocytes, macrophages, and granulocytes (11). In order to separate GMPs (Ly-6C-) from GPs (Ly-6C+) and cMOP/MPs (Ly-6C+) , you can use Ly-6G in the lineage mix, instead of Gr-1 which recognizes both Ly-6C and Ly-6G.

 

Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34+

CD135 (Flt3)-

CD16/32hi

Ly-6C-

CD115 (CSF-1R)-

GP (Granulocyte Progenitor)

GPs are oligopotent progenitors derived from GMPs. This progenitor gives rise to neutrophils and possibly other granulocytic lineages such as basophils and eosinophils.

 

Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Ly-6G-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34+

CD135 (Flt3)-

CD16/32hi

Ly-6C+

CD115 (CSF-1R)-

cMOP/MP (Common Monocyte Progenitor/Monocyte Progenitor)

cMOP/MPs are oligopotent progenitor cells derived from GMPs and MDPs. cMOP/MPs differentiate to Ly-6Chi and Ly-6Clow monocytes which can differentiate further into macrophages and dendritic cells.


Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Ly-6G-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34+

CD135 (Flt3)-

CD16/32hi

Ly-6C+

CD115 (CSF-1R)+

MDP (Monocyte-Dendritic Cell Progenitor)

MDPs are oligopotent progenitors which give rise to monocytes and dendritic cell populations (cDC1, cDC2, pDC). The relationship between MDPs and other progenitor populations is not fully understood.


Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1- or Ly-6G-, CD11c-, NK1.1-)

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34+

CD135 (Flt3)+

Ly-6C-

CD115 (CSF-1R)+

CDP (Common-Dendritic Cell Progenitor)

CDPs are oligopotent progenitors derived from Monocyte-Dendritic Cell Progenitors (MDPs). They give rise to all dendritic cell populations (pDC, cDC1, and cDC2) via subsequent differentiation into Pre-cDCs (Precursor of Conventional Dendritic Cells ) and Pre-pDCs (Precursor of Plasmacytoid Dendritic Cells).


Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1- or Ly6G-, CD11c-, NK1.1-)

CD117 (c-kit)int/low

Sca-1 (Ly-6A)-

CD34+

CD135 (Flt3)+

CD115 (CSF-1R)+

CLP (Common Lymphoid Progenitor)

CLPs are multipotent progenitors derived from Lymphoid Multipotent Progenitors (LMPPs). It gives rise to all lymphoid lineages including T cells, B cells and NK cells.


Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1- ,CD11c-, NK1.1-)

CD117 (c-kit)int/low

CD135 (Flt3)+

CD127 (IL-7Rα)+

Pre-pDC (Precursor of Plasmacytoid Dendritic Cells)

Pre-pDCs are unipotent progenitors which give rise to pDCs. It is believed that pre-pDCs are derived either from CDPs or LMPPs likely through the CLP stage.


Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Gr-1- ,CD11c-, NK1.1-)

CD117 (c-kit)int/low

CD135 (Flt3)+

CD115 (CSF-1R)-

CD127 (IL-7Rα)-

Pre-cDC (Precursor of Conventional/Classical Dendritic Cells)

Pre-cDCs are derived from CDPs and give rise to classical/conventional dendritic cell populations, cDC1 and cDC2s. In mice, several pre-cDC subsets have been identified with varying expression of Siglec-H and Ly6C. Siglec-H and Ly6C serve as lineage markers that can distinguish pre-cDC subpopulations committed to the either the cDC1 (Siglec-H-Ly6C-) or cDC2 lineages (Siglec-H-Ly6C+) (14).


Mouse Markers:

Lin- (Ter119-, CD3-, CD45R/B220- or CD19-, CD11b-, Ly6G-, NK1.1-)

CD117 (c-kit)low

CD11clow

MHC IIlow

CD135 (Flt3)+

CD172a (SIRPα)low

pDC (Plasmacytoid Dendritic Cell)

pDCs are derived from Pre-pDC s in the bone marrow. pDCs play key role in antiviral responses and produce IFN type I cytokines.


Mouse Markers:

Lin- (Ter119-, CD3-, CD19-, NK1.1-)

CD11c+

Siglec H+

CD45R/B220+

CD317 (BST2)+

 

Learn more about DC subtypes, essential markers for phenotyping, and DC function with our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

cDC1 (Conventional/Classical Dendritic Cell I)

cDC1s, also known as CD8α+ DCs, are derived from Pre-cDCs in the bone marrow. cDC1s one of the key antigen presenting cells responsible for cross-presenting antigens to CD8+ T cells and priming of Th1 and Treg cells.


Mouse Markers:

Lin- (Ter119-, CD3-, CD19-, NK1.1-)

CD11chi

MHC IIhi

CD24+

CD8a+

CD370 (CLEC9a, DNGR1)+

CD11blow

CD172a (Sirp1α)low

 

Learn more about DC subtypes, essential markers for phenotyping, and DC function with our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

cDC2 (Conventional/Classical Dendritic Cell II)

cDC2s, also known as CD11b+ DCs, are derived from Pre-cDCs at steady-state or from monocytes during inflammation in the tissue. cDC2s are one of the key antigen presenting cells responsible for priming of Th1, Th2 and Th17 cells.


Mouse Markers:

Lin- (Ter119-, CD3-, CD19-, NK1.1-)

CD11chi

MHC IIhi

CD24+

CD8alo/-

CD370 (CLEC9a, DNGR1)lo/-

CD11b+

CD172a (Sirp1α)+

 

Learn more about DC subtypes, essential markers for phenotyping, and DC function with our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

Tissue Resident Dendritic Cells

Tissue-resident dendritic cells are derived from Pre-cDCs during steady-state or from monocytes during inflammation in the tissue. Tissue-resident cells are subcategorized into CD103+ and CD11b+ cells.


Mouse Markers:

CD45+

CD11chi

MHC IIhi

CD11b+/-

CD103+/-

 

To learn more about heterogeneity, tissue distribution, and the function of dendritic cell subsets check out our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

Macrophage (Mφ)

Macrophages are a part of the mononuclear phagocytic system. They play a critical role in inflammatory responses involving bacterial infections and tissue injuries. Originally, tissue-resident macrophages are derived from the embryonic precursor in the yolk sac. In adulthood, the peripheral pool of macrophages is maintained by monocytes.


Mouse Markers:

MerTK+

F4/80+

CD11b+

CD172a (SIRPα)+

CD68+

 

Learn more about macrophage heterogeneity, function, and phenotypic markers on our Macrophage Webpage .

Basophil

Basophils belong to a subclass of granulocytes differentiated in the bone marrow from the GMP precursor. Basophils circulate in the blood and control allergy responses by performing different functions, including production of histamine and regulation of IgE levels via secretion of IL-4 cytokine.


Mouse Markers:

SSChi

CD200R3+

FcεRIα+

Eosinophil

Eosinophils belong to a subclass of granulocytes differentiated in the bone marrow from the GMP precursor. eosinophils have been shown to play an essential role in parasite infections (i.e. helminth infection) and some allergic reactions including asthma. eosinophils are potent mediators of T helper responses by production of Th1 (i.e., IL-4, IL-5, IL-9, IL-13, IL-25) and Th2 (IL-12, IFN-γ) cytokines.


Mouse Markers:

SSChi

CD11b+

Siglec-F+

F4/80+

CD125 (IL-5Rα)+

CD193 (CCR3)+

Neutrophil

Neutrophils are the most abundant leukocytes circulating in the blood. The lifespan of neutrophils is very short. The daily replenishment of the neutrophil peripheral pool happens via differentiation of neutrophils from GPs in the bone marrow. neutrophils patrol blood vessels, scavenging for pathogen-derived antigens and are one of the primary innate immune subsets to be recruited to sites of inflammation where they produce a plethora of antimicrobial peptides and proteins including α-defensins, lysozymes, and lactoferrin.


Mouse Markers:

SSChi

Ly6G+

Ly-6G/Ly-6C (Gr-1)+

CD11b+

Ly6Clow/-

CD16/32 (FCγRIII)+

LC (Langerhans Cell)

LCs are members of dendritic cell family and serve as antigen presenting cells in the skin. Unlike other dendritic cell types, LCs are derived from progenitors residing in the yolk sac during embryogenesis. In adulthood, the peripheral pool of LCs can be replenished by monocytes.


Mouse Markers:

CD45+

CD11c+

MHC II+

CD207 (Langerin)+

CD324 (E-Cadherin)+

CD326 (EpCAM)+

CD205+

CD11b+

 

Learn more about Langerhans cells and other DC subtypes with our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

Microglia

Microglia are specialized antigen presenting cells identified in brain parenchyma. Microglia cells are derived from erythromyeloid progenitors in the yolk sac during primitive hematopoiesis around embryonic day 7.5-8 (E7.5-8). At steady-state, microglia cells are responsible for the removal of dead neurons and Aβ peptides, secretion of trophic factors such as BDNF, and synapse pruning. Under inflammatory signals, microglial cells become activated and differentiate into effective APCs.


Mouse Markers:

CD45low

CD11c- (upregulated upon activation)

MHC IIlow (upregulated upon activation)

P2RY12+

Iba-1+

CD68low

MerTK+

F4/80+

CD11b+

CX3CR1+

 

Learn more about Microglia cells and other myeloid cells in the CNS with our Dendritic Cell Webpage and Microglia Webpage.

Ly6Chi Monocyte (Classical Monocyte or Inflammatory Monocyte)

Monocyte development includes several precursor cells including GMPs, MDPs, and cMOPs. Upon inflammatory stimuli, Ly6Chi monocytes migrate into inflamed tissues where they secrete pro-inflammatory mediators (i.e., TNF-α, iNOS, IL-12, type 1 interferons) and give rise to inflammatory M1 macrophages and dendritic cells.


Mouse Markers:

SSCint

Ly6Chi or Gr-1int

CD115+

CD11b+

F4/80int

CX3CR1+

CCR2hi

CD43+

 

Learn more about monocyte heterogeneity, function, and phenotypic markers on our Monocyte Webpage.

Ly6Clow Monocyte (Non-classical or Resident Monocyte)

Ly6Clow monocytes are derived from either Ly6Chi monocytes or directly from upstream progenitors such as cMOPs. At steady-state, Ly6Clow monocytes patrol blood vessels. During inflammation, they can enter tissue and develop into anti-inflammatory M2 macrophages eliciting wound repair.


Mouse Markers:

SSCint

Ly6Clow or Gr-1low

CD115+

CD11b+

F4/80int

CX3CR1hi

CCR2+

CD43hi

 

Learn more about monocyte heterogeneity, function, and phenotypic markers on our Monocyte Webpage .

HSC (Hematopoietic Stem Cell)

HSCs are pluripotent cells which give rise to all blood cell populations of lymphoid, myeloid, and erythroid lineages and persist throughout the lifespan. They have the potential to self-renew to sustain the stem cell pool or differentiate into other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells (1-3, 5, 6).

 

Human Markers:

Lin- (CD3-,CD19-, CD56-, CD10-, CD14-, CD66b-, CD335-, CD11c-)

CD45RA-

CD34+

CD38-

CD90+

CD135 (Flt3)+

MPP (Multipotent Progenitor)

MPPs are multipotent progenitors derived from HSCs. They can give rise to other multipotent progenitor (LMPPs), or oligopotent and unipotent progenitors (i.e., CMPs, GMPs, or MDPs), which give rise to terminally differentiated cells of lymphoid, myeloid and erythroid lineages (1-3, 5, 6).

 

Human Markers:

Lin- (CD3-,CD19-, CD56-, CD10-, CD14-, CD66b-, CD335- , CD11c-)

CD34+

CD38-

CD90-

CD45RA-

CD135 (Flt3)+

LMPP (Lymphoid-Primed Multipotent Progenitor)

LMPPs are multipotent progenitors derived from MPPs. They generate all cells in the lymphoid lineage and pDCs.

 

Human Markers:

Lin- (CD3-,CD19-, CD56-, CD14-, CD66b-, CD335-, CD11c-)

CD34+

CD38-

CD90-

CD45RA+

CD10-

CD135 (Flt3)+

MLP (Multi Lymphoid Progenitor)

MLPs are multipotent progenitors derived from LMPPs. They generate all cells in the lymphoid lineage and pDCs.

 

Human Markers:

Lin- (CD3-,CD19-, CD56-, CD14-, CD66b-, CD335- , CD11c-)

CD34+

CD38-

CD45RA+

CD10+

CD7+

CD90-

CD135 (Flt3)+

CMP (Common Myeloid Progenitor)

CMPs are oligopotent progenitors derived from MPPs. This progenitor can differentiate into erythroid and myeloid lineages.

 

Human Markers:

Lin- (CD3-,CD19-, CD56-, CD14-, CD66b-, CD335-, CD11c-)

CD34+

CD38+

CD90-

CD45RA-

CD10-

CD123int

CD135 (Flt3)+

GMDP (Granulocyte/Monocyte/Dendritic Cell Progenitor)

GMDPs are oligopotent progenitors including GMPs. GMDPs originate from CMPs and have potential to differentiate to neutrophils (and possibly eosinophils and basophils), monocytes, and all dendritic cell populations.


Human Markers:

Lin- (CD3-,CD19-, CD56-, CD10-, CD14-, CD66b-, CD335- , CD11c-)

CD117 (c-kit)hi

CD34+

CD38+

CD45RA+

CD123int

CD135 (Flt3)+

CD115 (CSF-1R)-

CD116 (GM-CSFRα)-

CD11c-

HLA-DR+

CD33+

GMP (Granulocyte-Monocyte Progenitor)

GMPs are oligopotent progenitors derived from CMPs. Recent studies have shown that GMPs are a heterogeneous population of cells containing oligopotent progenitors such as GMDPs, MDPs, and CDPs. GMDPs differentiate to all myeloid lineages including mono/macs, granulocytes (neutrophils, basophils, and eosinophils), and dendritic cells, while MDPs and CDPs give rise to monocytes and dendritic cells or only dendritic cells, respectively (5).


Human Markers:

Lin- (CD3-,CD19-, CD56-, CD14-, CD66b-, CD335- , CD11c-)

CD34+

CD38+

CD90-

CD45RA+

CD123hi/low

CD135 (Flt3)+

CD10-

CD115 (CSF-1R)+/-

CD116 (GM-CSFRα)+/-

MDP (Monocyte-Dendritic Cell Progenitor)

MDPs are oligopotent progenitors derived from GMDPs which give rise to monocytes/macrophages and dendritic cell populations.

 

Human Markers:

Lin- (CD3-,CD19-, CD56-, CD10-, CD14-, CD66b-, CD335-)

CD34+

CD38hi

CD45RA+

CD123int

CD135 (Flt3)+

CD115 (CSF-1R)+

CD116 (GM-CSFRα)-

CD11clow/-

HLA-DR+

CD33+

CDP (Common-Dendritic Cell Progenitor)

CDPs are oligopotent progenitors derived from MDPs. They give rise to all dendritic cell populations via subsequent differentiation into Pre-cDCs.


Human Markers:

Lin- (CD3-,CD19-, CD56-, CD10-, CD14-, CD66b-, CD335-)

CD34+

CD38hi

CD45RA+

CD123hi

CD135 (Flt3)+

CD115 (CSF-1R)-

CD116 (GM-CSFRα)hi/low

CD11c+

HLA-DR+

CD33+

Pre-cDC (Precursor of Conventional/Classical Dendritic Cells)

Pre-cDCs are derived from CDPs. They give rise to both classical/conventional CD141+ and CD1c+ dendritic cell populations.


Human Markers:

Lin- (CD3-,CD19-, CD56-, CD10-, CD14-, CD66b-, CD335-)

CD34-

CD38+

CD45RA+

CD123int

CD135 (Flt3)+

CD115 (CSF-1R)-

CD116 (GM-CSFRα)+

CD11c+

HLA-DR+

CD33+

pDC (Plasmacytoid Dendritic Cell)

pDCs are derived from LMPPs. They play a key role in antiviral responses and are a major producers of IFN type I cytokines.


Human Markers:

Lin- (CD3-,CD20-, CD66b-, CD335-)

CD45RAhi

CD303 (BDCA-2)+

CD123hi

CD11clow

 

Learn more about DC subtypes, essential markers for phenotyping and DC function with our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

Tissue Resident Dendritic Cells

Tissue-resident dendritic cells are derived from pre-cDCs (Precursor of Conventional DCs) during steady-state or from monocytes during inflammation in the tissue. In some tissues, like intestine, tissue-resident cells are subcategorized into CD103+ or CD11b+ cells. In the dermis, tissue-resident cells can be subcategorized based on CD14 expression.


Human Markers:

CD45+

CD141 (BDCA-3)+/-

CD103+/-

XCR1+/-

CD1c (BDCA-1)+/-

CD11c+

HLA-DR+

 

Learn more about DC subtypes, essential markers for phenotyping and DC function on our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

Macrophage (Mφ)

Macrophages are a part of the mononuclear phagocytic system. They play a critical role in inflammatory responses involving bacterial infections and tissue injuries. Originally, tissue-resident macrophages are derived from the embryonic precursor in the yolk sac. In adulthood, the peripheral pool of macrophages is maintained by monocytes.


Human Markers:

CD11b+

CD64+

CD68+

 

Learn more about macrophage heterogeneity, function, and phenotypic markers on our Macrophage Webpage .

CD141+ DC (Conventional/Classical CD141+ Dendritic Cell)

CD141 (BDCA-3)hi DCs are derived from Pre-cDCs in the bone marrow. CD141 (BDCA-3)hi DCs are equivalent to the mouse cDC1 population and are one of the key antigen presenting cells responsible for cross-presenting antigens to CD8+ T cells and priming T helper responses.


Human Markers:

Lin- (CD3-,CD20-, CD66b-, CD335-)

CD141 (BDCA-3)hi

CD370 (CLEC9A, DNGR1)+

CD172a (SIRPα)-

CD1c (BDCA-1)-

CD11c+

HLA-DR+

 

Learn more about DC subtypes, essential markers for phenotyping and DC function on our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

CD1c+ DC (Conventional/Classical CD1c+ Dendritic Cell)

CD1c (BDCA-1)+ DCs are derived from Pre-cDCs during steady-state or from monocytes during inflammation in the tissue. CD1c (BDCA-1)+ DCs are equivalent to mouse cDC2s and are one of the key antigen presenting cells responsible for priming Th, Th2, and Th17 cells.


Human Markers:

Lin- (CD3-,CD20-, CD66b-, CD335-)

CD141 (BDCA-3)-

CD370 (CLEC9A, DNGR1)-

CD172a (SIRPα)+

CD1c (BDCA-1)+

CD11c+

HLA-DR+

 

Learn more about DC subtypes, essential markers for phenotyping, and DC function on our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

Basophil

Basophils are a subclass of granulocytes which are differentiated in the bone marrow from GMPs. Basophils circulate in blood and control allergy responses by performing different functions including production of histamine and control of IgE levels via secretion of IL-4.


Human Markers:

SSChi

FcεRIα+

IL-5Rα+

CD203c+

Integrin Β7+

CD193 (CCR3)+

Eosinophil

Eosinophils are a subclass of granulocytes which are differentiated in the bone marrow from GMPs. Eosinophils have been shown to play an essential role in parasite infections (i.e. helminth infection) and some allergic reactions including asthma. Eosinophils are potent mediators of T helper responses by production of Th1 (i.e., IL-4, IL-5, IL-9, IL-13, IL-25) and Th2 (IL-12, IFN-γ) cytokines.


Human Markers:

SSChi

FcεRIα-

IL-5Rα+

CD203c+

Integrin Β7+

CD193 (CCR3)+

Neutrophil

Neutrophils are the most abundant leukocytes circulating in the blood. The lifespan of neutrophils is very short and the daily replenishment of the peripheral pool of neutrophils occurs via differentiation of Neutrophils from GPs in the bone marrow. Neutrophils patrol blood vessels scavenging for pathogen-derived antigens and are one of the primary innate immune subsets to be recruited to the sites of inflammation where they produce antimicrobial peptides and proteins including α-defensins, lysozymes, and lactoferrin.


Human Markers:

SSChi

CD66b+

CD15+

IL-5Rα-

CD203c-

CD193 (CCR3)-

Integrin Β7-

FcεRIα-

LC (Langerhans Cell)

LCs are the members of dendritic cell family and serve as an antigen presenting cells in the skin. In comparison to other dendritic cell types, LCs are derived from progenitor residing in yolk sac during embryogenesis. In adulthood, the peripheral pool of LCs can be replenished by monocytes.


Human Markers:

CD45+

HLA-DR+

CD207 (Langerin)+

CD324 (E-Cadherin)+

EpCAM+

CD1a+

 

Learn more about Langerhans cells and other DC subtypes on our Dendritic Cell Webpage and Dendritic Cell Interactive Pathway.

Microglia

Microglia are specialized antigen presenting cells in brain parenchyma. Microglia cells are derived from erythromyeloid progenitors in the yolk sac during primitive hematopoiesis. During steady-state microglia cells are responsible for the removal of dead neurons and Aβ peptides, secretion of trophic factors such as BDNF, and synapse pruning. Under inflammatory signals, microglial cells become activated and differentiate into effective APCs.


Human Markers:

HLA-DR+

CD68+

Iba1+

 

Learn more about Microglia cells and other myeloid cells in the CNS on our Dendritic Cell Webpage and Microglia Webpage.

CD14+ Monocyte (Classical Monocyte or Inflammatory Monocyte)

Several precursor cells are involved in monocyte development including GMPs, GMDPs, and MDPs. CD14+ monocytes are equivalent to the mouse Ly6Chi monocyte which, upon inflammatory stimuli, migrate into inflamed tissues where they secrete proinflammatory mediators (i.e., TNF-alpha, iNOS, IL-12, and IFN type I cytokines) and give rise to inflammatory M1 macrophages and dendritic cells.


Human Markers:

SSCint

CD115+

CD14+

CD16-

CX3CR1+

CCR2hi

CD64+

HLA-DR+

 

Learn more about monocyte heterogeneity, function, and phenotypic markers on our Monocyte Webpage .

CD16+ Monocyte (Non-classical or Resident Monocyte)

Several precursor cells are involved in monocyte development including GMPs, GMDPs, and MDPs. CD16+ monocytes are equivalent to mouse Ly6Clo monocytes which patrol blood vessels. During inflammation, they can enter tissue and presumably develop into anti-inflammatory M2 macrophages eliciting wound repair.


Human Markers:

SSCint

CD115+

CD14-

CD16+

CX3CR1hi

CCR2+

HLA-DR+

 

Learn more about monocyte heterogeneity, function, and phenotypic markers our our Monocyte Webpage .

B Cells

T Cells

 
 
 

 

LT-HSC (Long-Term Hematopoietic Stem Cell)

LT-HSCs are pluripotent cells which give rise to all blood cell populations of lymphoid, myeloid, and erythroid lineages and persist throughout the entire lifespan. They have the potential to self-renew sustaining the stem cell pool or differentiate into ST-HSCs and other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells.

 

Mouse Markers:

Lin- (Ter119-, CD3-, B220- or CD19-, CD11b-, Gr-1-, CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34-

CD135 (Flt3)-

CD150 (SLAM)+

ST-HSC (Short-Term Hematopoietic Stem Cell)

ST-HSCs are multipotent progenitors with a short-term renewal potential as compared to LT-HSCs. It is believed that ST-HSCs differentiate from the daughter cell during an asymmetrical division of LT-HSCs. ST-HSCs can give rise to other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells of lymphoid, myeloid and erythroid lineages.

 

Mouse Markers:

Lin- (Ter119-, CD3-, B220- or CD19-, CD11b-, Gr-1-, CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)-

CD150 (SLAM)-

MPP (Multipotent Progenitor)

MPPs are multipotent progenitors derived from ST-HSCs. They can give rise to another multipotent progenitor, LMPPs, or oligopotent and unipotent progenitors which give rise to terminally differentiated cells.


Mouse Markers:

Lin- (Ter119-, CD3-, B220- or CD19-, CD11b-, Gr-1-, CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)low

CD150 (SLAM)-

LMPP (Lymphoid-Primed Multipotent Progenitor)

LMPPs are responsible for the generation of lymphocytes and pDCs through subsequent differentiation steps including CLPs and pre-pDCs respectively. LMPPs were originally thought to be a homogeneous population of precursors containing multipotent cells with the equal potential to differentiate into several lymphoid lineages. However, a recent study has demonstrated that LMPP is a heterogeneous population of cells comprising unipotent clones with a non-overlapping lineage differentiation potential(21).

 

Mouse Markers:

Lin- (Ter119-, CD3-, B220- or CD19-, CD11b-, Gr-1-, CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)hi

CD150 (SLAM)-

CD127 (IL-7Rα)-

CLP (Common Lymphoid Progenitor)

CLPs are multipotent progenitors derived from Lymphoid Multipotent Progenitors (LMPPs). They give rise to all lymphoid lineages including T cells, B cells and NK cells.

 

Mouse Markers:

Lin- (Ter119-, CD3-, B220- or CD19-, CD11b-, Gr-1- ,CD11c- , NK1.1- )

CD117 (c-kit)int/low

CD135 (Flt3)+

CD127 (IL-7Rα)+

Pre-pro B cell

Pre-pro B cells are differentiated from CLPs and are the earliest B cell progenitor identified in the bone marrow.


Mouse Markers:

CD117 (c-kit)-

CD127 (IL-7Rα)+

CD19-

CD24low/-

CD43-

CD45R (B220)low

IgM-

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, SPI1 (PU.1)+

Pro-B cell

Pro-B cells are differentiated from Pro-pre B cells. Upregulation of RAG1/RAG2 recombinases induces rearrangement of the D and J segments of the µ-heavy chain in these cells. Meanwhile, TdTs (Terminal Deoxynucleotidyl Transferases) add N- and P- nucleotides to the end of the D and J segments to diversify the specificity of newly forming B cell receptor.


Mouse Markers:

CD117 (c-kit)-

CD127 (IL-7Rα)+

CD19+/-

CD24low

CD43+

CD45R (B220)low

IgM-

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, SPI1 (PU.1)+

Late Pro-B cell

Late Pro-B cells undergo rearrangement of the V segment of the µ-heavy chain. Upon V segment rearrangement, it joins the DJ segments to form a mature µ-heavy chain. Late Pro-B cells which have successfully rearranged a heavy chain that is capable of pairing with surrogate light chains (VpreB and λ5) to form a pre-BCR (B cell receptor) are allowed to progress to the next stage.

 

Mouse Markers:

CD117 (c-kit)-

CD127 (IL-7Rα)+

CD19+

CD20+

CD24+

CD43+

CD45R (B220)low

IgM-

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, SPI1 (PU.1)+

Pre-B cell

Upon upregulation of the pre-BCR on the surface of Pre-B cells, the expression of RAG1/2 recombinases is downregulated and Pre-B cells undergo several divisions before they enter the Late Pre-B cell stage.


Mouse Markers:

CD117 (c-kit)-

CD127 (IL-7Rα)+

CD19+

CD20+

CD24+

CD43low

CD45R (B220)+

Surface IgM-

Cytoplasmic μ heavy chain+

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Late Pre-B cell

After a second wave of RAG1 and RAG2 recombinase upregulation, Pre-B cells undergo V and J segment rearrangement and diversification to form λ and κ light chains. Upon successful pairing of light chain with the µ-heavy chain, the B cell receptor associates with Ig-α and Ig-β molecules to form a fully functioning receptor.


Mouse Markers:

CD117 (c-kit)-

CD127 (IL-7Rα)+

CD19+

CD20+

CD24+

CD43-

CD45R (B220)+

IgM-

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Immature B cell

Immature B cells expressing a newly formed IgM/BCR (B Cell Receptor) undergo a negative selection process in which B cells expressing BCRs with a high affinity for self-antigens are eliminated or undergo additional receptor editing to change the antigen specificity. Immature B cells egress the bone marrow to continue their differentiation in blood and other lymphoid organs.


Mouse Markers:

CD127 (IL-7Rα)+

CD19+

CD20+

CD23-

CD24+

CD43-

CD45R (B220)+

IgM+

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

T1 B cell (Transitional Type 1 B cell)

T1 B cells differentiate from immature B cells which have successfully passed negative selection. Transitional B cell maturation occurs primarily in the spleen, with T1 B cells present in the red pulp. Upon encountering antigen, T1 B cells differentiate to T2 B cells which are able to give rise to follicular, marginal zone, germinal center, memory, and plasma B cells.


Mouse Markers:

CD127 (IL-7Rα)+

CD19+

CD20+

CD22+

CD23-

CD24+

CD45R (B220)+

IgMhi

IgDlow/-

CD93+

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

T2 B cell (Transitional Type 2 B cell)

T2 B cells can be identified in spleen follicles. T2 B cells can differentiate further into either circulating B cells which cluster into GCs or non-circulating B cells that populate the marginal zones.


Mouse Markers:

CD127 (IL-7Rα)+

CD19+

CD20+

CD22+

CD23+

CD24+

CD45R (B220)+

IgMhi

IgD+

CD93+

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Mature B cell

Mature B lymphocytes develop sequentially from transitional type 1 (T1) and type 2 (T2) precursors in the spleen. They can be distinguished from their progenitors by expression of both IgM and IgD, as well as a lack of Immature B cell marker CD24. Mature B cells can further differentiate into germinal center and marginal zone B cells.


Mouse Markers:

CD127 (IL-7Rα)+

CD19+

CD20+

CD22+

CD23+

CD24low/-

CD45R (B220)hi

IgM+

IgD+

CD93-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

FO B cell (Follicular B cell)

Follicular B cells can be found within structures called follicles (which contain germinal centers) in secondary and tertiary lymphoid organs such as the spleen, Peyer's patches, and lymph nodes. Unlike marginal zone B cells, Follicular B cells circulate throughout the body. They are capable of becoming either Memory B cells or Plasma cells. In most instances, these cells require T cells for full activation.


Mouse Markers:

CD19+

CD20+

CD21/35low

CD22+

CD23+

CD38+

CD45R (B220)hi

IgMlow

IgD+

CD93-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

GC B cell (Germinal Center B cell)

Upon antigen encounter and interaction with T follicular cells, B cells cluster into germinal centers within follicles. B cell maturation in GCs is associated with somatic hypermutation of antibody V regions allowing the cells to generate antibodies with high avidity BCRs. Antigen selected GC B cells leave the germinal center to differentiate further into memory or plasma B cells.


Mouse Markers:

CD19+

CD20+

CD38+

CD45R (B220)+

IgM+

IgD+/-

IgA+

IgG+

GL7+

CD95+

PNA+

 

Transcription Factors: Pax-5+ , XBP-1+, IRF4+, Bcl-6+

MZ B cell (Marginal Zone B cell)

Marginal Zone (MZ) B cells are non-circulating B cells which can be identified in the marginal zone of lymphoid organs such as the spleen. They typically have a lower threshold of activation compared to follicular B cells and can develop into plasma cells with the help of T cells.


Mouse Markers:

CD19+

CD20+

CD21/35+

CD22+

CD23+

CD45R (B220)hi

IgM+

IgDlow

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Memory B cell

Memory B cells are found predominantly in the marginal zone of the spleen, the sub-capsular sinus of the lymph nodes, and under the intestinal epithelium in Peyer's patches and crypt epithelium of the tonsils. Memory B cells develop after infection and retain memory of the antigen allowing for a more rapid immune response upon reintroduction of the antigen.


Mouse Markers:

CD19+

CD20+

CD27+

CD38+/-

CD45R (B220)hi

IgM+

IgD-

IgA+

IgG+

CD138-

 

Transcription Factors: Pax-5+ , POU2AF1 (OBF1)+, SPI-B+

Plasma B cell

Plasma B cells are terminally differentiated B cells which circulate throughout the body and produce large volumes of antibodies. They can be identified by high levels of expression of CD27 and CD138.


Mouse Markers:

CD19low

CD20low

CD21/35-

CD23-

CD27hi

CD38low

CD45R (B220)low

IgM-

IgD-

CD138+

CD184 (CXCR4)hi

 

Transcription Factors: Blimp-1+, XBP-1+, IRF4+

Plasmablast

Plasmablasts are located in the peripheral immune organs where they undergo rapid proliferation to produce a large pool of terminally differentiated plasma cells. They can be distinguished from plasma cells by low production antibodies, ability to proliferation, and a shorter lifespan.


Mouse Markers:

CD19+

CD20+

CD27hi

CD38hi

CD45R (B220)+

IgM+/-

IgD+/-

IgA+/-

IgG+/-

CD138-

Transitional B cell

Transitional B cells are immature B cell progenitors derived from fetal hematopoietic progenitors which are capable of differentiating to B1 B cells.


Mouse Markers:

CD19+

CD20+

CD21/35+/-

CD23+/-

CD24+

CD45R (B220)+

IgM+

IgDlow

CD93+

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

B1-a/b B cell

B1 cells are derived from fetal progenitors and are localized mainly in the peritoneal cavity and gut-associated lymphoid tissues. B1-a and B1-b cells can be distinguished by the expression of CD5. The B1 BCR is less diverse than that of B2 cells as it is rearranged from a limited number of Ig gene segments and lacks nucleotide editing. B1 cells predominantly secrete IgM and undergo very little somatic hypermutation.


Mouse Markers:

CD19+

CD20+

CD23-

CD43+

CD45R (B220)+

IgM+

IgDlow

CD5+/-

CD1d+

CD11b+

Breg (Regulatory B cell)

Regulatory B cells represent a small fraction of B cells with immunosuppressive capacities. These cells can be phenotypically challenging to identify, as they bear many common markers found on other B cell types.


Mouse Markers:

CD19+

CD20+

CD21/35hi/mid

CD23+/-

CD45R (B220)+

IgM+

IgD+/-

CD5+

CD1dhi

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

HSC (Hematopoietic Stem Cell)

HSCs are pluripotent cells which give rise to all blood cell populations of lymphoid, myeloid, and erythroid lineages and persist throughout the lifespan. They have the potential to self-renew to sustain the stem cell pool or differentiate into other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells (1-3, 5, 6).

 

Human Markers:

Lin- ( CD3-, CD19-, CD56-, CD10-, CD14-, CD66b-, CD335-, CD11c- )

CD45RA-

CD34+

CD38-

CD90+

CD135 (Flt3)+

MPP (Multipotent Progenitor)

MPPs are multipotent progenitors derived from HSCs. They can give rise to other multipotent progenitor (LMPPs), or oligopotent and unipotent progenitors (i.e., CMPs, GMPs, or MDPs), which give rise to terminally differentiated cells of lymphoid, myeloid and erythroid lineages (1-3, 5, 6).


Human Markers:

Lin- ( CD3-, CD19-, CD56-, CD10-, CD14-, CD66b-, CD335- , CD11c- )

CD34+

CD38-

CD90-

CD45RA-

CD135 (Flt3)+

LMPP (Lymphoid-Primed Multipotent Progenitor)

LMPPs are multipotent progenitors derived from MPPs. They generate all cells in the lymphoid lineage and pDCs.

 

Human Markers:

Lin- ( CD3-, CD19-, CD56-, CD14-, CD66b-, CD335- , CD11c- )

CD34+

CD38-

CD90-

CD45RA+

CD10-

CD135 (Flt3)+

MLP (Multi Lymphoid Progenitor)

MLPs are multipotent progenitors derived from LMPPs. They generate all cells in the lymphoid lineage and pDCs.

 

Human Markers:

Lin- ( CD3-, CD19-, CD56-, CD14-, CD66b-, CD335- , CD11c- )

CD34+

CD38-

CD45RA+

CD10+

CD7+

CD90-

CD135 (Flt3)+

Pro-B cell

Pro B cells are differentiated from MLPs and are one of the earliest B cell progenitors identified in the bone marrow. Upregulation of RAG1/RAG2 recombinases induces the rearrangement of the V, D, and J segments of the µ-heavy chain. Meanwhile, TdT (Terminal Deoxynucleotidyl Transferase) adds N- and P- nucleotides to the end of the V, D, and J segments to diversify the specificity of the newly forming BCR. Pro-B cells which successfully rearrange the heavy chain capable of pairing with the surrogate light chains (VpreB and λ5) to form a pre-BCR are able to differentiate further.


Human Markers:

CD34+

CD38+

CD10+

CD127 (IL-7Rα)+

CD19+

CD20+

CD24+

IgM-

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, SPI1 (PU.1)+

Pre-B cell

After the second wave of RAG1 and RAG2 recombinase upregulation, Pre-B cells undergo V and J segment rearrangement and diversification to form λ and κ light chains. Upon successful pairing of a light chain with the µ-heavy chain, the BCR associates with Ig-α and Ig-β molecules to form a fully functioning receptor.


Human Markers:

CD34-

CD38+

CD10+

CD127 (IL-7Rα)+

CD19+

CD20+

CD24+

Surface IgM-

Cytoplasmic μ heavy chain+

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Immature B cell

Immature B cells expressing the newly formed IgM/BCR undergo a negative selection process in which B cells expressing BCRs with a high affinity to self-antigens are eliminated or undergo additional receptor editing to change the antigen specificity. Immature B cells egress the bone marrow to continue their differentiation in blood and other lymphoid organs.


Human Markers:

CD10+

CD127 (IL-7Rα)+

CD19+

CD20+

CD24hi

IgM+

IgD-

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Transitional B cell

Transitional B cells differentiate from immature B cells which successfully pass negative selection. Transitional B cell maturation occurs primarily in the spleen. Upon encountering antigen, Transitional B cells differentiate to follicular, marginal zone, germinal center, memory, and plasma B cells.


Human Markers:

CD10lo

CD127 (IL-7Rα)+

CD19+

CD20+

CD21+

CD24hi

CD38hi

IgM+

IgDlo

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Naïve Mature B cell

Mature B-lymphocytes develop from transitional B cell precursors in the spleen. They can be distinguished from their progenitors by expression of both IgM and IgD. Mature B cells can be further differentiated to germinal center and marginal zone B cells.


Human Markers:

CD10+

CD127 (IL-7Rα)+

CD19+

CD20+

CD24+

IgM+

IgD+

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

FO B cell (Follicular B cell)

Follicular B cells can be found within structures called follicles (which contain germinal centers) in secondary and tertiary lymphoid organs like the spleen, Peyer's patches, and lymph nodes. Unlike marginal zone B cells, follicular B cells circulate throughout the body. They are capable of becoming either memory B cells or plasma cells. In most instances, these cells require T cells for full activation.


Human Markers:

CD10-

CD127 (IL-7Rα)+

CD19+

CD20+

CD21+

CD22+

CD23+

CD38lo

IgMlo

IgD+

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

GC B cell (Germinal Center B cell)

Upon antigen encounter and interaction with T follicular cells, B cells cluster into germinal centers within follicles. B cell maturation in GCs is associated with somatic hypermutation of antibody V regions allowing to generate the antibodies with high avidity BCRs. Antigen selected GC B cells leave the germinal center to differentiate further to memory or plasma B cells.


Human Markers:

CD19+

CD20+

CD23+

CD38hi

IgM+

IgD+/-

IgA+

IgG+

 

Transcription Factors: Pax-5+ , XBP-1+ , IRF4+, Bcl-6+

MZ B cell (Marginal Zone B cell)

Marginal Zone (MZ) B cells are non-circulating B cells which can be identified in the marginal zone of lymphoid organs such as the spleen. They typically have a lower threshold of activation compared to follicular B cells and can develop into plasma cells with the help of T cells.


Human Markers:

CD19+

CD20+

CD21hi

CD23+/-

IgM+

IgDlo

 

Transcription Factors: E2A+, Pax-5+ , EBF1+, Oct2+

Memory B cell

Memory B cells are found predominantly in the marginal zone of the spleen, the sub-capsular sinus of the lymph nodes, and under the intestinal epithelium in Peyer's patches and crypt epithelium of the tonsils. Memory B cells develop after infection with a host and retain memory of the antigen allowing for a more rapid immune response upon reintroduction of the host.


Human Markers:

CD19+

CD20+

CD23lo

CD27+

CD38-

IgM+

IgD-

IgA+

IgG+

CXCR4+

 

Transcription Factors: Pax-5+, POU2AF1 (OBF1)+, SPI-B+

Plasma B cell

Plasma B cells are terminally differentiated B cells which circulate throughout the body and produce large volumes of antibodies. They can be identified by high levels of expression of CD27 and CD138.


Human Markers:

CD19lo

CD20-

CD27hi

CD38hi

IgM-

IgD-

CD138+

CXCR4+

 

Transcription Factors: Blimp-1+, XBP-1+ , IRF4+

Plasmablast

Plasmablasts are located in the peripheral immune organs where they undergo rapid proliferation to produce a large pool of terminally differentiated plasma cells. They can be distinguished from plasma cells by low production antibodies, ability to proliferation, and a shorter life-span.


Human Markers:

CD19+

CD20+

CD27hi

CD38hi

IgM+ /-

IgD+ /-

IgA+ /-

IgG+ /-

CD138-

CLP (Common Lymphoid Progenitor)

CLPs are multipotent progenitors derived from Lymphoid Multipotent Progenitors (LMPPs). They give rise to all cells from the lymphoid lineage including T cells, B cells, and NK cells.


Mouse Markers:

Lin- (Ter119-, CD3-, B220- or CD19-, CD11b-, Gr-1- ,CD11c- , NK1.1- )

CD117 (c-kit)int/low

CD135 (Flt3)+

CD127 (IL-7Rα)+

ILC1 (Group 1 Innate Lymphoid Cells)

Like T cells, ILCs are derived from CLPs; however, they do not respond in an antigen-specific manner. Group 1 ILCs include Natural Killer (NK) cells and produce type 1 cytokines including IFN-γ and TNF-α. They play a critical role in protecting the host against pathogens and tumor cells.


NK Cell Mouse Markers

NK1.1+

NKp46+   

CD11b+   

CD49b+

CD122 (IL-2Rβ)+

CD244 (2B4)+

CD314 (NKG2D)+


NK Cell Transcription factors: T-bet, Id2, Nfil3


ILC1 Mouse Markers:

Lin- (CD3-, CD11b-, B220-, Gr1-, Ter119-)

CD4-

CD8-

CD127 (IL-7Rα)+

IL-12Rβ+


ILC1 Transcription factors: T-bet


Learn more about NK and ILC cell development and function on our Natural Killer Cells and Innate Lymphoid Cells webpages.

ILC2 (Group 2 Innate Lymphoid Cells)

Like T cells, ILCs are derived from CLPs; however, they do not respond in an antigen-specific manner. Group 2 ILCs produce cytokines normally associated with Th2 cells including IL-5 and IL-13. They play a key role in response to helminth infection, allergic lung inflammation, and are involved in wound healing.


ILC2 Mouse Markers:

Lin- (CD3, CD11b-, B220-, Gr1-, Ter119-)

CD4-

CD8-

CD127 (IL-7Rα)+

CD90 (Thy1)+

CD117+

Ly6A (Sca-1)+

CD25+

ICOS+

IL-17Rβ+


ILC2 Transcription factors: RORα, GATA-3


Learn more about Innate Lymphoid cell development and function on our Innate Lymphoid Cells webpage.

ILC3 (Group 3 Innate Lymphoid Cells)

Like T cells, ILCs are derived from MLPs; however, they do not respond in an antigen-specific manner. Group 3 ILCs were originally discovered as cells that express NKp46, but do not resemble normal NK cells. Instead, they express RORγt and produce IL-17 and IL-22. ILC3s primarily reside in mucosal tissues where they help maintain intestinal homeostasis. Lymphoid tissue inducer cells (LTi) are considered subset of group 3 ILCs that are involved in lymphoid organ formation during embryogenesis. The exact relationship between LTis and other ILC3s is still being investigated.

 

ILC3 Mouse Markers:

Lin- (CD3, CD11b-, B220-, Gr1-, Ter119-)

CD4-

CD8-

NKp46+

CD127 (IL-7Rα)+

CD90 (Thy1)+

CD121a (IL-1R)+

IL-23R+


ILC3 Transcription factors: RORγt


Learn more about Innate Lymphoid cell development and function on our Innate Lymphoid Cells webpage.

ETP/DN1 (Early T Cell Progenitor/Double Negative Thymocyte 1)

ETP/DN1s are one of the first T cell progenitor populations that have been identified in the thymus. These progenitors are named double negative as they do not express the CD4 or CD8 co-receptors found on mature T cells. Additionally, they do not express the CD3/TCR complex.


Mouse Markers:

TCRαβ-

TCRγδ-

CD3-

CD4-

CD8α-

CD8β-

CD25-

CD44+

DN2 (Double Negative Thymocyte 2)

DN2 thymocytes are differentiated from DN1 progenitors. These progenitors were named double negative as they do not express the CD4 or CD8 co-receptors found on mature T cells. At this stage, upregulation of RAG1/RAG2 recombinases induces VDJ rearrangement of the β-chain and γδ- loci of the TCR. Meanwhile, TdTs (Terminal Deoxynucleotidyl Transferases) add N- and P- nucleotides to the end of the V, D and J segments to diversify the specificity of the newly forming T cell receptor. Determination of the αβ/γδ lineage fate depends on TCR signal strength. This model of lineage determination predicts that the γδ TCR transduces a stronger signal directing cells to the γδ lineage, while a pre-TCR transduces a weaker signal directing progenitors to the αβ lineage (25, 28).


Mouse Markers:

TCRαβ-

TCRγδ-

CD3-

CD4-

CD8α-

CD8β-

CD25+

CD44+

DN3 (Double Negative Thymocyte 3)

DN3 thymocytes are differentiated from DN2 progenitor cells. These progenitors were named double negative as they do not express the CD4 or CD8 co-receptors found on mature T cells. DN3 T cells which have successfully rearranged a TCRβ-chain that is capable of pairing to a surrogate TCRα-chain pass the β-selection checkpoint and undergo clonal division before transitioning to the DN4 stage.


Mouse Markers:

TCRαβ-

TCRγδ-

CD3-

CD4-

CD8α-

CD8β-

CD25+

CD44-

DN4 (Double Negative Thymocyte 4)

DN4 thymocytes are differentiated from DN3 progenitor cells. These progenitors were named double negative as they do not express the CD4 or CD8 co-receptors found on mature T cells. DN4 cells undergo rearrangement of the TCR α-locus to form a functional αβ-TCR.


Mouse Markers:

TCRαβ-

TCRγδ-

CD3-

CD4-

CD8α-

CD8β-

CD25-

CD44-

ISP (Intermediate Single Positive Thymocyte)

ISP thymocytes form an intermediate stage between DN4s and DPs. During this stage, the TCRα-chain undergoes rearrangement to form the αβ-TCR before transitioning to the DP stage.


Mouse Markers:

TCRαβ-

TCRγδ-

CD3-

CD8+

DP (Double Positive Thymocyte)

DP thymocytes differentiate from the ISP stage and can be distinguished by the expression of both CD4 and CD8 co-receptors. The fate of DP cells depends on the interaction of their αβ-TCR with MHCI/II molecules expressed on cortical epithelial cells. Upon TCR interaction with self pMHC molecules, there are 3 possible outcomes:

  1. No Signal: DP thymocytes that receive no signal die of neglect.
  2. Weak signal: DP cells pass positive selection and transition to a CD4+CD8low stage before differentiating to single positive CD4 and CD8 T cells (28).
  3. High Affinity: To avoid potential autoimmunity, DP thymocytes expressing high avidity TCRs differentiate to FOXP3+ Treg cells, CD8αα IELs, or are subjected to clonal deletion through the process of negative selection (28, 27).

 

Alternatively, DP thymocytes that express a rearranged Va14i-TCR interact with glycolipids presented on CD1d molecules and differentiate into NKT cells (23).


Mouse Markers:

TCRαβlow/-

CD3low/-

CD4+

CD5+/-

CD8α+

CD8β+

CD69+/-

CD8αα IELs (CD8αα Intraepithelial Lymphocytes)

CD8αα IELs differentiate as an alternative pathway to clonal deletion of autoreactive T cells. Autoreactive DP cells which do not receive a costimulation signal through B7/CD28 escape clonal deletion during the process of negative selection in the thymic medulla. These cells downregulate both CD4 and CD8 co-receptors to become TCRαβ+ DN cells. From here, they migrate to gut tissues where they differentiate to CD8αα IELs and function to regulate intestinal homeostasis and maintain epithelial barrier function (27).


Mouse Markers:

TCRαβ+

CD3+

CD8α+

CD8b-

Transcription factors: Runx3

γδ-T cells

γδ-T cells diverge from αβ-T cells at the DN2 progenitor stage. γδ-T cells represent a small subset of T cells found in tissues of both lymphoid and non-lymphoid origin. Unlike the αβ-TCR, the γδ-TCR recognizes lipid antigens and doesn’t require antigen presentation by MHC molecules.


Mouse Markers:

CD3+

TCRαβ-

TCRγδ+

 

Transcription factors: SOX13

CD4+CD8low

CD4+CD8low cells differentiate from DP thymocytes through positive selection. CD4+CD8low thymocytes pass lineage commitment and differentiate into CD8+ and CD4+ T cells. According to the kinetic signaling model, the lineage fate decision depends on the persistence of TCR signaling in CD4+CD8low cells. Persistence of TCR signaling in CD4+CD8low intermediate thymocytes block IL-7 signaling and induces differentiation into CD4+ T cells. Cessation or disruption of TCR signaling permits IL-7 signaling resulting in co-receptor reversal and differentiation to CD8+ cells (28).


Mouse Markers:

TCRαβlow

CD3low

TCRγδ-

CD4+

CD8αlow

CD8βlow

CD8 Single Positive Thymocyte

CD8+ T cells or cytotoxic T cells differentiate from CD4+CD8low progenitors and recognize antigens presented on MHC class I molecules. Mature CD8+ T cells which are ready to egress the thymus can be identified by downregulation of CD24 and overexpression of S1PR.


Mouse Markers:

TCRαβ+

CD3+

CD4-

CD8α+

CD8β+

CD24+/-

S1PR+/-

 

Transcription factors: Runx3

CD4 Single Positive Thymocyte

CD4+ T cells or T helper cells differentiate from the CD4+CD8low progenitors and recognize antigens presented on MHC class II molecules. Mature CD4+ T cells which are ready to egress the thymus can be identified by downregulation of CD24 and overexpression of S1PR. In the periphery, mature CD4+ T cells differentiate into different T helper subsets upon encountering an antigen.


Mouse Markers:

TCRαβ+

CD3+

CD4+

CD8α-

CD8β-

CD24+/-

S1PR+/-


Transcription factors: TH-POKGATA-3


Learn more about T helper subsets on our T helper types webpage.

Treg

T regulatory cells are specialized T cells responsible for protecting the organism from autoimmune responses by regulating CD4+ and CD8+ T cell cytotoxic activity. One of the transcription factors important for Treg cell differentiation is FOXP3. Mice with the “Scurfy” mutation of the FOXP3 gene leading to ablation of FOXP3 expression exhibit multi-system autoimmune disorders.


Mouse Markers:

TCRαβ+

CD3+

CD4+

CD5+

CD25+

Helios+

CD134 (OX40)+

CD137 (4-1BB)+

CD152 (CTLA)

CD279 (PD-1)+

CD304 (Neuropilin)+

CD357 (GITR)+

 

Transcription factors: FOXP3Helios


Learn more on our T regulatory cell webpage.

iNKT (Invariant Natural Killer T cells)

DP thymocytes that express a rearranged Va14i-TCR interact with glycolipids presented on CD1d molecules and differentiate into NKT cells (23).


Mouse Markers:

CD1d tetramer+

Vα14+

CD3+

CD4+/-

CD24-

CD44+

 

Transcription factors: PLZF


Learn more about different stages of iNKT development and function on our Natural Killer T Cells webpage

MLP (Multi Lymphoid Progenitor)

MLPs are multipotent progenitors derived from LMPPs. They generate all cells in the lymphoid lineage and pDCs.


Human Markers:

Lin- ( CD3-, CD19-, CD56-, CD14-, CD66b-, CD335- , CD11c- )

CD34+

CD38-

CD45RA+

CD10+

CD7+

CD90-

CD135 (Flt3)+

ILC1 (Group 1 Innate Lymphoid Cells)

Like T cells, ILCs are derived from MLPs; however, they do not respond in an antigen-specific manner. Group 1 ILCs include Natural Killer (NK cells) and produce type 1 cytokines including IFN-γ and TNF-α. They play a critical role in protecting the host against pathogens and tumor cells.


NK Cell Human Markers

CD56+

CD3-

CD314 (NKG2D)+


NK Cell Transcription factors: T-bet , Id2, Nfil3


ILC1 Human Markers:

IL-1R+

CD56+

CD127(IL-7Rα)-

NKp30+

NKp44+

NKp46+


ILC1 Transcription factors: T-bet


Learn more about NK and ILC cell development and function on our Natural Killer Cells and Innate Lymphoid Cells webpages.

ILC2 (Group 2 Innate Lymphoid Cells)

Like T cells, ILCs are derived from MLPs; however, they do not respond in an antigen-specific manner. Group 2 ILCs produce cytokines normally associated with Th2 cells including IL-5 and IL-13. They play a key role in response to helminth infection, allergic lung inflammation, and are involved in wound healing.


ILC2 Human Markers:

CD45hi

IL-7Rα+

CD161+

CRTH2+


ILC2 Transcription factors: RORα, GATA-3


Learn more about Innate Lymphoid cell development and function on our Innate Lymphoid Cells webpage.

ILC3 (Group 3 Innate Lymphoid Cells)

Like T cells, ILCs are derived from MLPs; however, they do not respond in an antigen-specific manner. Group 3 ILCs were originally discovered as cells that express NKp46 but do not resemble normal NK cells. Instead, they express RORγt and produce IL-17 and IL-22. ILC3s primarily reside in mucosal tissues where they help maintain intestinal homeostasis. Lymphoid tissue inducer cells (LTi) are considered subset of group 3 ILCs that are involved in lymphoid organ formation during embryogenesis though the exact relationship between LTis and other ILC3s is still being investigated.

 

ILC3 Human Markers:

CD117 (c-Kit)+

CD127 (IL-7Rα)+

NKp44+/-

NKp46+/-

IL-1R+

IL-23R+


ILC3 Transcription factors: RORγt


Learn more about Innate Lymphoid cell development and function on our Innate Lymphoid Cells webpage.

ETP/DN1 (Early T Cell Progenitor/Double Negative Thymocyte 1)

ETP/DN1s are one of the first T cell progenitor populations that have been identified in the thymus. These progenitors are named double negative as they do not express the CD4 or CD8 co-receptors found on mature T cells. Additionally, they do not express the CD3/TCR complex.


Human Markers:

TCRαβ-

TCRγδ-

CD1α-

CD3-

CD4-

CD8α-

CD8β-

CD7-

CD10-

CD34+

DN2 (Double Negative Thymocyte 2)

DN2 thymocytes are differentiated from DN1 progenitors. These progenitors were named double negative as they do not express the CD4 or CD8 co-receptors found on mature T cells. At this stage, upregulation of RAG1/RAG2 recombinases induces VDJ rearrangement of the β-chain and γδ- loci of the TCR. Meanwhile, TdTs (Terminal Deoxynucleotidyl Transferases) add N- and P- nucleotides to the end of the V, D and J segments to diversify the specificity of the newly forming T cell receptor.

In mice, the αβ/γδ lineage fate depends on TCR signal strength. The signal strength model predicts that the γδ TCR transduces a stronger signal directing cells to the γδ lineage, while a pre-TCR transduces a weaker signal directing progenitors to the αβ lineage (25, 29,30).


Human Markers:

TCRαβ-

TCRγδ-

CD1α-

CD3-

CD4-

CD8α-

CD8β-

CD7+

CD10-

CD34+

DN3 (Double Negative Thymocyte 3)

DN3 thymocytes are differentiated from DN2 progenitor cells. These progenitors were named double negative as they do not express the CD4 or CD8 co-receptors found on mature T cells. DN3 T cells which have successfully rearranged a TCRβ-chain that is capable of pairing to a surrogate TCRα-chain pass the β-selection checkpoint and undergo clonal division before transitioning to the ISP stage. Alternatively, DN3 thymocytes which have a rearranged γδ-TCR continue their differentiation towards the γδ-T cells.


Human Markers:

TCRαβ-

TCRγδ-

CD1α+

CD3-

CD4-

CD8α-

CD8β-

CD7+

CD34+

ISP (Intermediate Single Positive Thymocyte)

ISP thymocytes form an intermediate stage between DN3s and DPs. During this stage, the TCRα-chain undergoes continued rearrangement to form the αβ-TCR before transitioning to the DP stage.


Human Markers:

TCRαβ-

TCRγδ-

CD1α+

CD3-

CD4+

CD8α-

CD8β-

DP (Double Positive Thymocyte)

DP thymocytes differentiate from the ISP stage and can be distinguished by the expression of both CD4 and CD8 co-receptors. The fate of DP cells depends on the interaction of their αβ-TCR with MHCI/II molecules expressed on cortical epithelial cells. Upon TCR interaction with self pMHC molecules, there are 3 possible outcomes:

  1. No Signal: DP thymocytes that receive no signal die of neglect.
  2. Weak signal: DP cells pass positive selection and transition to single positive CD4 and CD8 T cells (28).
  3. High Affinity: To avoid potential autoimmunity, DP thymocytes expressing high avidity TCRs differentiate to FOXP3+ Treg cells or are subjected to clonal deletion through the process of negative selection.

 

Alternatively, DP thymocytes that express a rearranged Va24i-TCR interact with glycolipids presented on CD1d molecules and differentiate into NK-T cells (23).


Human Markers:

CD3lo/-

TCRαβlo/-

CD4+

CD8α+

CD8β+

γδ-T cells

γδ-T cells diverge from αβ-T cells at the DN2 progenitor stage. γδ-T cells represent a small subset of T cells found in tissues of both lymphoid and non-lymphoid origin. Unlike the αβ-TCR, the γδ-TCR recognizes lipid antigens and doesn’t require antigen presentation by MHC molecules.


Human Markers:

CD3+

TCRαβ-

TCRγδ+


Transcription Factors: Id3

CD8 Single Positive Thymocyte

CD8+ T cells or cytotoxic T cells differentiate from DP progenitors and recognize antigens presented on MHC class I molecules.


Human Markers:

CD3+

TCRαβ+

CD4-

CD8α+

CD8β+


Transcription Factors: Runx3STAT5

CD4 Single Positive Thymocyte

CD4+ T cells or T helper cells differentiate from DP progenitors and recognize antigens presented on MHC class II molecules. In the periphery, mature CD4+ T cells differentiate into different T helper subsets upon encountering an antigen.


Human Markers:

CD3+

TCRαβ+

CD4+

CD8α-

CD8β-


Transcription Factors: TH-POKGATA-3


Learn more about T helper subsets on our T helper types webpage.

Treg

T regulatory cells are specialized T cells responsible for protecting the organism from autoimmune responses by regulating CD4+ and CD8+ T cell cytotoxic activity. One of the transcription factors important for Treg cell differentiation is FOXP3. Mice with the “Scurfy” mutation of the FOXP3 gene leading to ablation of FOXP3 expression exhibit multi-system autoimmune disorders. The phenotype of Scurfy mice closely resembles human IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked) syndrome.


Human Markers:

CD3+

TCRαβ+

CD4+

CD25+

CD45RA+

CD127lo


Transcription Factors: FOXP3


Learn more on our T regulatory cell webpage.

iNKT (Invariant Natural Killer T cells)

DP thymocytes expressing the rearranged Va24i-TCR interact with glycolipids presented on CD1d molecules and differentiate into NK-T cells.


Human Markers:

CD1d tetramer+

Vα24+

CD3+

CD56+

CD28+

CD45RO+


Transcription Factors: PLZF


Learn more about different stages of iNKT development and function on our Natural Killer T Cells webpage.

Select a species to begin:
 
 

 

HSC (Hematopoietic Stem Cell)

HSCs are pluripotent cells which gives rise to all blood cell populations of lymphoid, myeloid, and erythroid lineages. HSCs persist throughout the life-span. They have the potential to self-renew to sustain the stem cell pool or differentiate into other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells (1-3, 5, 6).


Human Markers:

Lin- (CD3- ,CD19- , CD56- , CD10- , CD14- , CD66b-, CD335- , CD11c- )

CD45RA-

CD34+

CD38-

CD90+

CD135 (Flt3)+

 

MPP (Multipotent Progenitor)

MPPs are multipotent progenitors derived from ST-HSCs. They can give rise to another multipotent progenitor, LMPPs, or oligopotent and unipotent progenitors which give rise to terminally differentiated cells (1-3, 5, 6).


Human Markers:

Lin- (CD3- ,CD19- , CD56- , CD10- , CD14- , CD66b-, CD335- , CD11c- )

CD34+

CD38-

CD90-

CD45RA-

CD135 (Flt3)+

 

CMP (Common Myeloid Progenitor) MEP (Megakaryocyte-Erythrocyte Progenitor)

CMPs/MEPs are oligopotent progenitors derived from MPPs. This progenitor can differentiate into erythroid and myeloid lineages (1-3, 5, 6). Recent studies by Notta F et al., have shown that CMPs contain three distinct cellular fractions: F1 (CD71-CD110-), F2 (CD71+CD110-), F3 (CD71+CD110+) (35).


Human Markers:

Lin- (CD3- ,CD19- , CD56- , CD14- , CD66b-, CD335- , CD11c- )

CD34+

CD38+

CD90-

CD45RA-

CD10-

CD123int

CD135 (Flt3)+/-

 

BFU-E (Burst-Forming Unit-Erythroid)

BFU-Es are the first committed erythrocyte progenitors which can be identified within the MEP subpopulation (31,37).


Human Markers:

Lin- ( CD3- , CD19- , CD56- , CD14- , CD66b- , CD335- , CD11c-)

CD34+

CD38-

CD41-

CD123+

CD235a-

CD71lo

CD36-


Transcription factors: GATA1, TAL1 , KLF1, Ldb1

CFU-E (Colony-Forming Unit Erythroid)

CFU-Es are erythrocyte progenitors downstream of BFU-Es. They can be identified within the MEP subpopulation (31,37).


Human Markers:

Lin- (CD3- ,CD19- , CD56- , CD14- , CD66b-, CD335- , CD11c- )

CD34-

CD38-

CD41-

CD123+

CD235a-

CD71hi

CD36+


Transcription factors: STATs , GATA2, TAL1, NFE2, GFI-1B, KLF1, Ldb1

CFU-Meg (Colony-Forming Unit-Megakaryocyte)

CFU-Megs are megakaryocyte progenitors identified within the MEP subpopulation (31).


Human Markers:

Lin- (CD3- ,CD19- , CD56- , CD14- , CD66b-, CD335- , CD11c- )

CD34+

CD38-

CD41+

CD123+

CD235a-

proE (Proerythroblast)

ProEs are the first erythroid progenitor population of cell that begin to express GPA (34, 36, 37). ProEs are large, committed progenitors which comprise the first stage of erythroblast maturation.


Human Markers:

CD45-

CD235a+

α4 integrinhi

Band3-


Transcription factors: STATs , GATA2, TAL1, NFE2, GFI-1B, KLF1, Ldb1

BasoE (Basophilic Erythroblast), PolyE (Polychromatic Erythroblast), OrthoE (Orthochromatic Erythroblast)

In the adult, erythroid progenitor cells can be identified in the bone marrow in erythroblastic islands consisting of a macrophage surrounded by erythroblasts. The GPA+ erythroid compartment consists of morphologically distinct, nucleated precursors that progress from ProE to BasoE to PolyE to OrthoE. As these cells mature, they undergo morphological differences including a decrease in cell size and nuclear condensation and polarization. These distinct subsets can be distinguished by expression of Band3 and α4-integrin (32).


Human Markers:

CD45-

GPA+

Band3hi/lo

α4-integrinhi/lo


Transcription factors: STATs , GATA2, TAL1 , NFE2, GFI-1B, KLF1, FOXO, NFκB, Ldb1

Reticulocyte

Reticulocytes are immature erythrocytes that have undergone enucleation and have been released into the circulatory system. Unlike mature erythrocytes, reticulocytes retain some organelles, including mitochondria. Before maturing into an erythrocyte, reticulocytes undergo extensive membrane remodeling and cytoskeletal rearrangements. Because reticulocytes retain RNA content, fluorescent dyes that bind to RNA can be used to enumerate reticulocytes in the peripheral blood.


Human Markers:

CD45-

CD235a+

Thiazole Orange+

Erythrocyte

Erythrocytes are enucleated red blood cells which function primarily to transport oxygen and carbon dioxide. Erythrocytes are very short lived cells and are replenished from the reticulocyte pool every 24 hours (31, 32).


Human Markers:

CD45-

CD235a+

CD41-

FSClo

Megakaryocyte

Megakaryocytes are large bone marrow cell which are responsible for the production of platelets involved in thrombosis and hemostasis (31, 35).


Human Markers:

CD41+

CD42+

CD45-

Platelets

Platelets, derived from megakaryocytes, have an essential role in thrombosis and hemostasis. Platelets express CD41 and CD61 glycoproteins which form a gpIIb/IIIa (CD41/CD61) complex, also known as integrin αIIbβ3. This complex acts as the receptor for fibrinogen and fibronectin.

Upon platelet activation CD41/CD61 undergoes conformational changes. The Pac-1 clone can specifically distinguish the activation-induced conformational epitope of the complex. CD42b and CD62P can also help to distinguish resting versus activated platelets, respectively (33).


Human Markers:

CD45-

CD41/CD61+

CD42b+/-

CD62P+/-

LT-HSC (Long-Term Hematopoietic Stem Cell)

LT-HSCs are pluripotent cells which give rise to all blood cell populations of lymphoid, myeloid, and erythroid lineages and persist throughout the entire lifespan. They have the potential to self-renew sustaining the stem cell pool or differentiate into ST-HSCs and other multi-, oligo-, and unipotent progenitors which give rise to terminally differentiated cells.

 

Mouse Markers:

Lin- (TER-119-, CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34-

CD135 (Flt3)-

CD150 (SLAM)+

ST-HSC (Short-Term Hematopoietic Stem Cell)

ST-HSCs are multipotent progenitors with a short-term renewal potential as compared to LT-HSCs. It is believed that ST-HSCs differentiate from the daughter cell during an asymmetrical division of LT-HSCs. ST-HSCs can give rise to other multi, oligo-, and unipotent progenitors which give rise to terminally differentiated cells of lymphoid, myeloid and erythroid lineages.

 

Mouse Markers:

Lin- (TER-119-, CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)-

CD150 (SLAM)-

MPP (Multipotent Progenitor)

MPPs are multipotent progenitors derived from ST-HSCs. They can give rise to another multipotent progenitor, LMPPs, or oligopotent and unipotent progenitors which give rise to terminally differentiated cells.


Mouse Markers:

Lin- (TER-119-, CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)+

CD34+

CD135 (Flt3)low

CD150 (SLAM)-

 

CMP (Common Myeloid Progenitor)

CMPs are oligopotent progenitors derived from MPPs. This progenitor can differentiate into erythroid and myeloid lineages. It was originally believed that CMPs were a homogeneous population of precursor cells containing multipotent cells with the equal potential to differentiate into both myeloid and lymphoid lineages. However, a recent study has demonstrated that, instead, CMPs are a heterogeneous population of cellprogenitors which are comprised of unipotent clones with non-overlapping potential that give rise to erythroid, megakaryocytic or myeloid lineages. (11,12,13).


Mouse Markers:

Lin- (TER-119-, CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34+

CD135 (Flt3)+/-

CD150 (SLAM)+/-

CD105 (Endoglin)-

CD16/32low

 

MEP (Megakaryocyte-Erythrocyte Progenitor)

MEPs are oligopotent progenitors derived from CMPs which give rise to both megakaryocytes and erythrocytes. More recent studies have shown that MEPs are a heterogeneous population consisting of 4 progenitor populations: Pre MegE (CD105-CD150+), MkP (CD150+CD41 +), Pre CFU-E(CD150+CD105int), and CFU-E (CD150-CD105+) (13).


Mouse Markers:

Lin- (CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34-

CD135 (Flt3)-

CD150 (SLAM)+/-

CD105 (Endoglin)+/-

CD41+/-

CD16/32-

TER-119-

 

Pre MegE (Precursor of Megakaryocytes and Erythrocytes)

Pre MegE is a megakaryocyte/erythrocyte progenitor identified within the MEP population (13).


Mouse Markers:

Lin- (CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34-

CD150 (SLAM)+

CD105 (Endoglin)-

CD41-

CD16/32-

TER-119-

 

Pre CFU-E (Precursor of Colony-Forming Unit Erythroid)

Pre CFU-Es are erythrocyte progenitors identified within the MEP population (13).


Mouse Markers:

Lin- (CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34-

CD150 (SLAM)+

CD105 (Endoglin)int

CD41-

CD16/32-

TER-119-


Transcription factors: PU.1, GATA1, TAL1, KLF1, Ldb1

CFU-E (Colony-Forming Unit Erythroid)

CFU-Es are erythrocyte progenitors downstream of Pre CFU-E and can be identified within the MEP population (13).


Mouse Markers:

Lin- (TER-119-, CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34-

CD150 (SLAM)-

CD105 (Endoglin)+

CD41-

CD16/32-

TER-119-


Transcription factors: STATs , GATA1, TAL1, NFE2, GFI-1B, KLF1, Ldb1

MkP (Megakaryocyte Precursor)

MkPs are megakaryocyte progenitors identified within the MEP population (13).


Mouse Markers:

Lin- (CD3- , CD45R/B220- or CD19- , CD11b- , Gr-1- , CD11c- , NK1.1- )

CD117 (c-kit)hi

Sca-1 (Ly-6A)-

CD34-

CD150 (SLAM)+

CD105 (Endoglin)-

CD41+

CD16/32-

TER-119-


Transcription factors: RUNX1 , FLI1, GATA-1, GFI-1B

proE (Proerythroblast)

ProEs are the first erythroid progenitor population of cells that express TER-119 (34, 36, 37). ProEs are large, committed progenitors which comprise the first stage of erythroblast maturation.


Mouse Markers:

CD45-

TER-119lo

CD71hi

CD44hi

FSChi


Transcription factors: STATs , Gata1, Tal1, NFE2, GFI-1B, ELKF/KLF1, Ldb1

BasoE (Basophilic Erythroblast), PolyE (Polychromatic Erythroblast), OrthoE (Orthochromatic Erythroblast)

In the adult, erythroid progenitor cells can be identified in the bone marrow in erythroblastic islands consisting of a macrophage surrounded by erythroblasts. The TER-119+ compartment consists of morphologically distinct, nucleated precursors that progress from ProE to BasoE to PolyE to OrthoE. reticulocyte to mature red blood cells. As these cells mature, they undergo morphological differences including a decrease in cell size and nuclear condensation and polarization. These precursor subsets can be distinguished by a combination FSC and expression of CD44 or CD71 and TER-119 (34, 36, 37).


Mouse Markers:

TER-119lo/+

CD71hi/-

CD44hi/-

FSChi/lo

Reticulocyte

Reticulocytes are immature erythrocytes that have undergone enucleation and have been released into the circulatory system. Unlike mature erythrocytes, reticulocytes retain some organelles, including mitochondria. Before maturing into an erythrocyte, reticulocytes undergo extensive membrane remodeling and cytoskeletal rearrangements. Because reticulocytes retain RNA content, fluorescent dyes that bind to RNA can be used to enumerate reticulocytes in the peripheral blood.


Mouse Markers:

CD45-

TER-119+

Thiazole Orange+

Erythrocyte

Erythrocytes are enucleated red blood cells which function primarily to transport oxygen and carbon dioxide. Erythrocytes are very short lived cells and are replenished from the reticulocyte pool every 24 hours (31, 32).


Mouse Markers:

CD45-

TER-119+

CD71-

CD44-

FSClo

Megakaryocyte

Megakaryocytes are large bone marrow cells which are responsible for the production of platelets and are involved in thrombosis and hemostasis.


Mouse Markers:

CD41+

CD45-

TER-119-


Transcription factors: RUNX1 , FLI1, GATA-1, GFI-1B

Platelets

Platelets, derived from megakaryocytes, have an essential role in thrombosis and hemostasis. Inefficient platelet production and/or defective platelet function results in wide range of bleeding disorder pathologies.


Mouse Markers:

CD9+

CD45-

CD41+

CD62P+/-

TER-119-


Transcription factors: RUNX1 , FLI1

Myelopoiesis:
 

1. Breton G., et al. 2015. J. Exp. Med. Mar 9;212(3):401-13. PubMed  (Human pre-cDC)
2. Breton G., et al. 2015. Nat. Protoc. Sep;10(9):1407-22. PubMed (Human cord blood progenitors, myeloid cells)
3. Doulatov S., et al. 2010. Nat. Immunol. Jul;11(7):585-93. PubMed (Human Hematopoietic Progenitors)
4. Hettinger J., et al. 2013. Nat. Immunol. Aug;14(8):821-30. PubMed (Mouse MDPs)
5. Lee J., et al. 2015. J. Exp. Med. Mar 9;212(3):385-99. PubMed (Human GMDPs, GMPs, and CDPs).
6. Lee J., et al. 2017. Nat. Immunol. Aug;18(8):877-888. PubMed (Human Hematopoiesis)
7. Mori Y. et al. 2009. J. Exp. Med. Jan 16;206(1):183-93. PubMed (Human granulocytes)
8. Naik SH., et al. 2013. Nature. Apr 11;496(7444):229-32. PubMed (Mouse LMPPs)
9. Notta F., et al. 2016. Science. Jan 8;351(6269):aab2116. PubMed (Human Myeloerythroid progenitors and development).
10. Onai N., et al. 2013. Immunity. May 23;38(5):943-57. PubMed (Mouse pre-pDCs)
11. Paul F., et al. 2015. Cell. Dec 17;163(7):1663-77. PubMed (Mouse CMPs and GMPs)
12. Perié L., et al. 2015. Cell. Dec 17;163(7):1655-62. PubMed (Mouse CMPs)
13. Pronk C., et al. 2007. Cell Stem Cell. Oct 11;1(4):428-42. PubMed (Mouse myeloerythroid progenitors)
14. Schlitzer A., et al. 2015. Nat. Immunol. Jul;16(7):718-28. PubMed (Mouse pre-cDCs)
15. Seita J. and Weissman IL. 2010. Wiley Interdiscip. Rev. Syst. Biol. Med. Nov-Dec;2(6):640-53. PubMed (Mouse and Human Hematopoiesis)
16. Walker DG. and Lue L. 2015. Alzheimers Res. Ther. Aug 19;7(1):56. PubMed (Microglia)
17. Yanez A., et al. 2015 Blood. Feb 26;125(9):1452-9. PubMed (Mouse GPs and cMOP/MPs)

 

Lymphopoiesis:
 

18. Banerjee A., et al. 2016. PLoS One. May 11;11(5):e0155311. PubMed
19. Cambier JC., et al. 2007. Nat. Rev. Immunol. Aug;7(8):633-43. PubMed
20. Engel P., et al. 2011. Pharmacol. Rev. Mar;63(1):127-56. PubMed
21. Naik SH., et al. 2013. Nature. Apr 11;496(7444):229-32 PubMed (Mouse LMPPs)
22. Pieper K. 2013. J. Allergy Clin. Immunol. Apr;131(4):959-71. PubMed
23. Borowski C. and Bendelac A. 2005. J. Exp. Med. Mar 21;201(6):833-6. PubMed (Mouse iNKT)
24. Geiger TL. and  Sun JC. 2016. Curr. Opin. Immunol. Apr;39:82-9. PubMed (Mouse NK cell development)
25. Hayes SM., et al. 2005. Immunity. May;22(5):583-93. PubMed (T cell development)
26. Klose CSN., et al. 2018. Mucosal Immunol. Mar;11(2):333-344. PubMed (Mouse IELs)
27. Pobezinsky LA., et al. 2012. Nat. Immunol. Apr 29;13(6):569-78. PubMed (Mouse IELs)
28. Singer A., et al. 2008. Nat. Rev. Immunol. Oct;8(10):788-801. PubMed (Mouse T cell development)
29. Taghon T. and Rothenberg EV. Semin. Immunopathol. 2008 Dec;30(4):383-98. PubMed (Human T cell development)
30. Vicente R., et al. 2010. Semin. Immunol. Oct;22(5):270-5. PubMed (Human T cell development)

 

Megakaryopoiesis/Erythropoiesis:
 

31. Belay E., et al. 2015. Blood. Feb 5;125(6):1025-33. PubMed (Human erythroid progenitors)
32. Hu J., et al. 2013. Blood. Apr 18;121(16):3246-53 PubMed (Human erythroid progenitors)
33. Granja T. et al. 2015. Thromb. Res. Oct;136(4):786-96 PubMed (Human platelet phenotyping)
34. Liu J. et al., 2013. Blood. Feb 21;121(8):e43-9. PubMed (Mouse erythroblasts)
35. Notta F., et al. 2015. Science. Jan 8;351(6269):aab2116. PubMed (Human cord blood megakaryocyte/erythrocyte progenitors)
36. Palis J. 2014. Front. Physiol. Jan 28;5:3 PubMed (Mouse  erythroid progenitors)
37. Wickrema A., et al. 2007. Oncogene. Oct 15;26(47):6803-15. PubMed (Mouse/human erythroid transcriptional factors)
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