Stem Cell Markers

All life forms begin with stem cells, which are defined as cells that have the dual capacity to self-renew and to produce progenitors or different types of specialized cells in the organism. Scientists mainly work with two kinds of stem cells: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. One of the main problems in stem cell research is how researchers can identify and characterize a stem cell. In the past few years, people have developed a method of attaching the antibody molecule to another molecule (or tag) that has the ability to fluoresce when triggered by an energy source such as an ultraviolet light or laser beam. Now, there are a variety of fluorescent labels with emitted light that differs in color and intensity. Researchers utilize this chemical property of fluorescence and a unique receptor pattern on the cell surface to identify a specific number of stem cells. One method for using markers is a technique called fluorescence-activated cell sorting (FACS).

Embryonic Stem Cells

Embryonic stem cell (ESC) is described by its origin. It is obtained from the blastocyst stage of the embryo. Embryonic stem cells are unique cell populations with the capability of both self-renewal and differentiation, and thus ESCs can give rise to any type of adult cell.

Several methods have been applied to characterize ESCs, but the most widely used method is analysis of cell surface antigens by flow cytometry and evaluation of gene expression profile by RT-PCR or microarrays. Many of the cell surface antigens used to identify hESCs were initially detected with antibodies prepared against mouse or human embryonal carcinoma cells. Although the function of these antigens in the continuance of undifferentiated human embryonal carcinoma cells is not necessarily clear, they may represent helpful markers for the recognition of pluripotent stem cells.

Table 1. Surface markers expressed by embryonic stem cells.

MarkersHuman ES cellsMouse ES cells
SSEA-1+-
SSEA-3-+
SSEA-4-+
TRA-1-60-+
TRA-1-81-+
GCTM-2-+
Alkaline phosphatase++
Oct-4++
GDF-3+?

Haematopoietic Stem Cells

The stem cells that form blood and immune cells are known as haematopoietic stem cells (HSCs). HSCs are one of the best characterized adult stem cells and the only stem cells used in clinics. Since HSCs look and behave similarly to normal white blood cells during culture, it has been a challenge to identify them by morphology (size and shape). Even now, scientists have to rely on cell surface proteins, which generally serve as markers of white blood cells.

A variety of markers has been found to aid in distinguishing and separating HSCs. Although none of these markers recognize the activity of functional stem cells, it is possible to purify near-homogenous HSCs by combining typically with 3 to 5 different markers. The ability to obtain pure preparations of HSCs, albeit in limited numbers, has greatly contributed to the functional and biochemical characterization of these important cells.

Table 2. Proposed cell surface markers of undifferentiated haematopoietic stem cells.

MouseHuman
CD34low/-CD 34+
SCA-1+CD59+
Thy1+/lowThy1+
CD38+CD38low/-
C-kit+C-kit-/low

Mesenchymal Stem Cell

Stem cells from adult tissues are an important source for cell therapy, gene therapy and tissue engineering. These cells typically have limited lineage potential in comparison to embryonic stem cells, which can be advantageous in certain therapeutic applications from the standpoint of controlling cell growth and differentiation.

Specific diagnostic surface markers for human mesenchymal stem cells (hMSCs) have not been identified, however, several surface markers have been found to be commonly associated with hMSCs including STRO-1, CD105, CD166, and CD271.

Table 3. Mesenchymal stem cell markers.

 Surface antigens
PositiveCD13, CD29, CD44, CD49b, CD54, CD71, CD73, CD105, CD106, CD166
NegativeCD3, CD4, CD6, CD9, CD10, CD11a, b, CD14, CD15, CD34, CD45, D18, CD31, CD49d, CD50, CD62E, CD117, CD133

Neural Stem Cells

Neural stem cells (NSCs) have recently attracted widespread attention because of their inherent ability to generate all major types of cells of the nervous system. Therefore, NSCs are considered to be a potential resource for repairing and restoring the physiological functions of damaged, diseased or aging neural tissues.

The major research limitation is that the cell preparations used as a source of NSCs are themselves naturally heterogeneous and consisting of both NSCs and self-renewing, but more lineage restricted progenitors, thereby skewing the NSC studies to an unknown direction. In addition, there is increasing evidence that implies clear functional differences between neural stem and progenitor cells. Consequently, there is an urgent need to use strategies to identify and isolate pure populations of NSCs and other types of cells with the aim of resolving their shared or unique biological properties in cell-fate determination and lineage progression.

Table 4. Neural stem cell markers.

Neural stem cellsGFAP, Nestin, Prominin, SOX-2
Proliferating cellsKi-67, BrdU, PCNA
Immature neuronsbeta Tubulin, DCX, PSA-NCAM
Radial gliaGLAST, RC2
Mature neuronsNeuN, MAP-2, NF, BLBP
Oligodendrocyte precursorsNG2
OligdendrocytesO4, MBP, RIP

References

  1. Rao R. R. et al. Cell surface markers in human embryonic stem cells. Methods Mol Biol, 2007, 407: 51-61.
  2. Feng-Juan Lv, et al. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells, 2014, 32: 1408-1419.

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