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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