Stem cell biology has emerged as one of the most significant fields in contemporary science. Stem cells give rise to every other cell in the body and possess the ability to both self-renew and differentiate. In addition, scientists have been able to reprogram or induce the creation of pluripotent stem cells to further expand the possibilities in translational medicine. BioLegend offers stem cell-focused reagents for flow cytometry, cell screening, western blotting, ELISAs, cell differentiation, and more.

Stem Cell Concepts

 

Two main characteristics define stem cells: the ability to divide multiple times without differentiating (Self-Renewal) and the capacity to differentiate into specialized cell types (Potency). These terms are discussed below.

Obligatory Asymmetric Replication: the cell divides, maintaining the stem cell population with one copy and one differentiated daughter cell.


 

Stochastic Differentiation: one father stem cell divides into two differentiated daughter cells. In order to maintain the population, a second father cell divides into two stem cells.


 

Totipotency: totipotent cells are obtained from a joined sperm and egg cell, it can differentiate into embryonic and extraembryonic cells. It has the capacity to create a completely viable organism.

 

Pluripotency: pluripotent cells are derived from totipotent cellsand have the potential to differentiate into almost any cell (i.e., embryonic stem cells from blastocyst).

 

 

Embryonic Stem Cell

 

Multipotency: cells that can give rise to multiple cell types. These cells are typically closely related For example, Hematopoietic Stem Cell can change into several types of blood cells, but not brain cells.

 

 

Hematopoietic Stem Cell

 

Oligopotency: the cell can only differentiate into a few cell types (i.e., myeloid or lymphoid progenitor cells).

 

 

Common Lymphoid Progenitor

 

Unipotency:  it can only make one cell type: itself. It also has the power to self-renew (i.e., hepatocytes).

 

 

Hepatocytes

 

References:

  1. Appelbaum, F.R. et al. 2009. Thomas’ Hematopoietic Cell Transplantation. 4th ed. John Wiley & Sons.
  2. Dingli, D. et al. 2007. PLoS Comput. Biol. 3: e53.
  3. Lander, A.D. 2009. J. Biol. 8:70.
  4. Mitalipov, S., and Wolf, D. 2009. Adv. Biochem. Eng. Biotechnol. 114:185.

 

Typically derived from in vitro fertilized eggs destined for medical waste, ESCs are obtained from the inner cell mass(ICM) of the blastocyst. These cells are isolated before a portion of the ICM differentiates (post fertilization: 3.5 days in mice, 5 days in humans). With the proper signals, the cells can proliferate indefinitely without differentiating, even in vitro. These pluripotent cells can differentiate into ectoderm, mesoderm, or endoderm. Because of the ethical ramifications of their derivation, there is some controversy over the use of ESCs. However, they represent the most flexible and potent cells compared to stem cells obtained by other means. Given their unlimited potential, ESCs are a favorite among scientists in clinical and research settings.

 

References:

  1. Nishikawa, S.I. et al. 2007. Nat. Rev. Mol. Cell Biol. 8:502.
  2. Stojkovic, M. et al. 2004. Stem Cells. 22:790.
Pregnant
Bone Marrow: one of the first and most well-known stem cell niches, bone marrow houses the majority of hematopoietic stem cells. Isolation of cells from this area is generally very invasive and requires anesthesia.
Peripheral Blood: in recent years, hematopoietic stem cells (HSCs) have increasingly been isolated in the blood. They can be mobilized from the bone marrow by cytokine treatment. Typically, HSCs are selected for CD34. This type of isolation is far less intrusive than bone marrow isolation.
Umbilical Cord Blood (UCB): typically discarded following birth, the umbilical cord was discovered to be rich in hematopoietic stem cells (HSCs). UCB provides lower amounts of HSCs and is usually reserved for treatment of children.
Amniotic Fluid: multipotent stem cells have been isolated from pregnant women.

Other Notable Niches: Brain, Skeletal Muscle, Skin, Teeth, Heart, Gastrointestinal Tract, Liver, Pancreas, Testes

References:

  1. Gavrilov, S. et al. 2009. Curr. Stem Cell. Res. and Ther.. 4:81.
  2. Weaver, C.H. et al. 2001. Bone Marrow Transplant.. 27: S23.

Image of frozen, human induced pluripotent stem cells provided courtesy of Dr. Deepak Srivastava's lab.

Induced Pluripotent Stem Cells (iPSCs) are adult cells forced back into an embryonic cell-like state. This is typically done through genetic reprogramming. Mouse iPSCs were first made in 2006, while human iPSCs were not discovered until late 2007. Both human and mouse iPSCs expressed stem cell markers and demonstrated pluripotent characteristics, producing cells for all three germ layers. iPSCs are used in several applications, including drug development, disease modeling, and transplantation medicine. Currently, viruses are used to transfect non-pluripotent cells. Transfected genes are involved with pluripotency and include Oct 3/4, SOX-2, c-Myc, and Klf4. Cells are then typically selected for the expression of Nanog, a transcription factor associated with self renewal. While the use of viruses in this method must be confirmed to be safe for humans, this process provides a form of “devolution,” producing new uses for cells thought to be terminally differentiated.

 

References:

  1. Takahashi, K. and Yamanaka, S. 2006. Cell 126:663.
  2. Takahashi, K. et al. 2007. Cell 131:861.

Given the natural ability of stem cells to generate almost any cell type in the human body, scientists have focused on the use of stem cells in therapeutic applications. Degenerative diseases like Parkinson’s and Multiple Sclerosis are associated with defective neural cells and the loss of myelin . Following a heart attack or stroke, myocardial cells can be weakened or killed. Type 1 Diabetes, an autoimmune disease, targets insulin producing cells in the pancreas for destruction. Stem cells could have applications in all of these diseases, where they could be developed into replacement neural, heart, or beta cells. These treatments may even be able to avoid graft versus host disease problems, as the stem cells could be raised by the host, for the host. While these new fields of research must determine optimal methods for delivery and differentiation of the proper cell type, the results are encouraging and opening new avenues of thinking.

 

References:

  1. Boyle, A.J. et al. 2006. Circulation 114:339.
  2. Lipsett, M. and Finegood, D.T. 2001. Diabetes 51:1834.
  3. Perrier, A.L. et al. 2004. Proc. Natl. Acad. Sci. USA. 101:12543.

Neural Tube

For vertebrates, the Neural Tube is the precursor to the central nervous system in a developing embryo.

Markers:
CD15 CD288
CD49f CD349 (Human)
CD57 (Human) ABCG2 (Human)
CD81 Neuroglycan-C
CD95 (Human) Neuropilin-2
CD146 Notch-1
CD271 (Human)  

Embryonic Stem Cells

Embryonic Stem Cells (ESCs) are obtained from the inner cell mass (ICM) of the blastocyst. These pluripotent ESCs can differentiate into ectoderm, mesoderm, or endoderm cells.

Markers:
CD9 CCR4
CD15 Frizzled-5
CD24 GCTM-2
CD29 Oct-4
CD30 Podocalyxin
CD49f SSEA-3
CD133 (Mouse) SSEA-4 (Human)
SSEA-5 (Human) CD324 (Human)
TRA-1-60 (Human) CD338 (Human)
TRA-1-81 (Human)  

Ectoderm

The ectoderm is the outermost layer of cells from the blastocyst's inner cell mass. The nervous system, sensory organs, skin, and its related structures, all arise from the ectoderm.

Markers:
NCAM (Human)  
NOTCH 1  

Outer Ectoderm (Epidermis)

The Outer Ectoderm develops into the lens, cornea, epidermis, hair, nails, tooth epithelium, mouth and olfactory epithelium.

Markers:
CD71  
p63  

Neural Crest

Neural Crest cells are multipotent and migratory, developing into several different lineages, including melanocytes, cartilage, bone, smooth muscle, and the peripheral nervous system.

Markers:
CD49d  
CD57 (Human)  
CD271 (Human)  
Notch 1  

Primitive Streak

The Primitive Streak establishes bilateral symmetry in embryos. It will ultimately give rise to all three germ layers, providing all tissues of the adult organism.

Markers:
N/A  

Primitive Endoderm

The Primitive Endoderm is a precursor stage of the definitive endoderm, which will develop into organs of the viscera, like the lungs, intestines, and liver.

Markers:
CD325 (Human)  

Definitive Endoderm

The Definitive Endoderm gives rise to the epithelial lining of the respiratory and digestive tracts. It also develops into the pancreas, lungs, intestines, thyroid, liver, and thymus.

Markers:
CD184 
CD325 (N-Cadherin) 

Mesodermal Embryonic Stem Cells

Mesodermal Embryonic Stem Cells are responsible for developing into the cells of the mesoderm, which consists of connective tissue (mesenchyme), muscles, the membrane lining several body cavities, and non-epithelial blood cells.

Markers:
CD31  
CD34  
CD325 (Human)  
Sca-1  

Immature Mesoderm

Immature Mesoderm can develop into either Lateral or Paraxial Mesoderm. The former produces connective tissue, while the latter develops into myeloid and lymphoid lineages.

Markers:
N/A  

Paraxial Mesoderm

The Paraxial Mesoderm develops at the side of the neural tube. During development, this portion of mesoderm will develop into somites, or the segments of the body.

Markers:
N/A  

Lateral Mesoderm

Also known as the Lateral Plate Mesoderm, the Lateral Mesoderm forms the viscera, heart, and dermis. The Lateral Mesoderm cells also form budding limbs during embryo development.

Markers:
CD5 CD49f
CD10 (Human) CD54
CD13 (Human) CD71
CD14 CD72 (Human)
CD15 CD73
CD29 CD90
CD31 CD105
CD44 CD106
CD49d STRO-1 (Human)

Mesenchymal Stem Cell

Mesenchymal Stem Cells (MSCs) are multipotent stromal cells. They are capable of differentiating into osteoblasts, adipocytes, and chondrocytes.

Markers:
CD44 CD105
CD45(-) (Human) CD106
CD45(-) (Mouse) CD166 (Human)
CD45(-) (Rat) CD271 (NGFR)
CD54 (ICAM-1) CD349 (Frizzled-9)
CD73 STRO-1
CD90 TNAP

Hemangioblasts

Hemangioblasts are multipotent cells capable of developing into hematopoietic and endothelial cells.

Markers:
CD31 CD202b
CD34 CD309
CD133 (Mouse) CD324 (Human)
CD143 (Human) Eph84
CD144 Podocalyxin

Endothelial Cells

Endothelial Cells are a thin layer of cells that line the inner surface of blood and lymphatic vessels. It serves as a physical barrier for the bloodstream and is involved with angiogenesis.

Markers:
CD31  
CD34  
CD62E (Human)  
CD105  
CD106  

Common Myeloid Progenitors

Common Monocyte Progenitors (CMPs) give rise to erythroid, megakaryocyte, and granulocyte lineages.

Markers:
CD34  
CD38  
CD45RA(-)  
CD123  

Common Lymphoid Progenitors

Common Lymphoid Progentiors (CLPs) give rise to B cells, T cells, plasmacytoid dendritic cells, and natural killer cells both in vitro and in vivo, but are incapable of generating myeloid cells.

Markers:
CD10 (Human)  
CD34  
CD38  

Granulocyte Monocyte Progenitors

Granulocyte Monocyte Progenitors (GMPs) give rise to basophils, eosinophils, neutrophils, and macrophages.

Markers:
CD34  
CD38  
CD45RA  
CD123  

Megakaryocyte Erythroid Progenitors

Derived from the Common Myeloid Progenitor, Megakaryocyte Erythroid Progenitors (MEPs) are the parent cells that give rise to megakaryocytes and erythrocytes.

Markers:
CD34  
CD38  
CD45RA(-)  
CD123(-)  

Megakaryoblasts

Megakaryoblasts are the precursors of thrombocytes, which are platelets.

Markers:
CD34  
CD36  
CD41  
CD61  
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