Stem cell markers

What are stem cells
Types of stem cells on the basis of origin
What are stem cells markers
Types of stem cell markers

1. MADE BY :- SADAF BEG STEM CELL MARKERS

2. What are stem cells? Stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely. It can divide and renew themselves over a long time. They have the potential to become specialized cells like muscle cells,blood vessels and brain cells. There are mainly two types of stem cells Embryonic stem cells Adult stem cells

3. Types of stem cells EMBRYONIC STEM CELL MULTIPOTENT PLURIPOTENT TOTIPOTENT 2. ADULT STEM CELL UNIPOTENT

4. Types of stem cell markers( based on the source of origin ) HAEMATOPOIETIC STEM CELLS Bone marrow MESENCHYMAL / MARROW STROMAL CELLS Bone marrow, Culture into osteoblasts NEURAL STEM CELLS Neurons, Astrocytes, Oligodendrocytes

5. WHAT ARE STEM CELL MARKERS? Stem cell markers are genes and their genes and their proteins products used by scientists to isolate and identify stem cells. Stem cells can also be identified by functional assays They are considered the gold standard for the identification and therapeutic purposes. Stem cell markers are given short hand names based on the molecules that it bind to the stem cell surface receptors. A cell that has the receptor stem cell antigen -1,on it’s surface, is identified as Sca-1.CD34 has been considered the most critical marker for haematopoietic stem cells (HSCs)

6. TYPES OF STEM CELL MARKERS Embryonic stem cell markers Cancer stem cell markers Osteoprogenitor stem cell markers Myogenic Precursor markers Neural stem cell markers Mesenchymal stem cell markers Intestinal stem cell markers Adipose- Derived stem cell markers Ovary and Tubal stem cell markers ectoderm and endoderm markers cytokeratin markers

7. EMBRYONIC STEM CELL MARKERS Embryonic stem cell (ESC) markers are molecules specifically expressed in ES cells. These markers are critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of embryonic stem cells. POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is expressed in totipotent embryonic stem and germ cells. A critical level of Oct-4 expression is required to sustain stem cell self-renewal and pluripotency. It is involved in the self-renewal of undifferentiated embryonic stem cells. It is a frequently used marker for undifferentiated cells. It is also the first and most recognized marker used for the identification of totipotent ES cells.

8. CELL SURFACE PLURIPOTENCY MARKERS TRA-1-60 and TRA-1-81 antigens on the human embryonal carcinoma (EC) cells and human pluripotent stem cell surfaces are widely used as markers in identifying and isolating ESCs Besides, they are also routinely used to assess the pluripotency status of induced pluripotent stem (iPS) cells. They are also expressed in teratocarcinoma and EG cells Both TRA-1-60 and SSEA4 are both expressed on human embryonal carcinomas and on human embryonic stem cells Upon differentiation, TRA-1-60 and SSEA4 expression levels decrease and SSEA1 expression increases on human embryonic stem cells over time when treated with Retinoic acid Besides, they also express CD349/frizzled-9, stage-specific embryonic antigen (SSEA)-4, Oct-4, Nanog, and nestin . Oct-4 and Nanog, as well as several cell surface markers (SSEA-1, SSEA-4, TRA-1-60, and TRA1-81) have been used to characterize mouse and human embryonic stem cells

9. Pluripotent embryonic stem cells (ESCs) correspond to cells within a developing embryo that have the capacity to generate all the embryonic germ layers (i.e. endoderm, mesoderm and ectoderm), and are able to give rise to all cell types in the body. ESCs may be derived from developing embryos at the pre-implantation blastocyst stage, and specifically from cells within the inner cell mass (ICM). In mice, the pluripotent state of ICM cells ( mESCs ) is often referred to as a “naïve” state. Following blastocyst implantation, ICM derived cells or mouse epiblast stem cells retain self-renewal capacity but are in a “primed” state of pluripotency. PLURIPOTENT EMBRYONIC STEM CELLS

10. CANCER STEM CELL MARKERS Cancer stem cells oncogenically transformed cancer stem cells (CSCs) are defined by their ability for self- renewal are defined by their ability for self-renewal and multipotency. The CSC hypothesis states that although CSCs represent a rare population of cells within a tumour, their high tumorigenic capacity drives tumorigenesis. Due to their intrinsic stem cell-like properties, CSC proliferation generates more CSCs and generates more CSCs and all the differentiated cell types that compose the bulk of the tumour. CD44 and CD24 have been used extensively in combinations or with other putative markers to isolate CSCs from solid tumours.

11. CANCER STEM CELL MARKER ORGAN CD44 BREAST CANCER HEAD AND NECK PROSTATE BRAIN COLON CD133 BRAIN PROSTATE COLON CD24 COLON,STOMACH, GALLBLADDER AND OVARY PANCREAS ALDH1 HEMATOPOIETIC BREAST

12. OSTEOPROGENITOR STEM CELL MARKER Bone homeostasis is a dynamic process relying on the balance of deposition by osteoblasts and resorption by osteocytes. Osteogenesis is not only responsible for the continuous remodelling Of bone tissue but also for the continuous remodelling of bone tissues but also crucial for the maintenance of bone tissue but also crucial for the maintenance of bone, size , shape and Integrity. Disruptions of bone homeostasis accompany disorders that include osteoporosis, arthritis, and many inheritable skeletal diseases. Cell type specific markers were developed to identify mesenchymal stem cells that have differentiated to osteoprogenitors, osteoblasts, or osteocytes. Certain osteoprogenitors can be distinguished by the expression pattern of TGF- beta bFGf, BMP- 2 and bFGF or gremlin 1. Certain markers like ALPP, MCAM , collagen I, collagen II, RUNX2, decorin , and TPO are also used . A Marconi et al use Sox5/6/9 as the markers for the perichondral progenitor cells.

13. OSTEOBLAST MARKERS Osteoblast are the skeletal cells which constitute the extracellular matrix of bone , typically arising in the embryo. The expression of osteoblastic markers ( CBFA-1/Runx2, ALP, SP7/ Osteria, M-CSF, AND RANK-L) supports the immunohistochemical findings. Immunofluorescence microscopy also revealed the existence of TRAP and MHC class II positive cells, suggesting the presence of osteoclasts and dendritic cells, respectively.

14. OSTEOCYTE MARKERS Osteocytes are the most abundant cells in bone, and their death by microdamage has been suggested to be the major event leading in the initiation of osteoclastic bone resorption . As osteocytes secrete several factors: TGF beta, RANKL, and MCSF which may affect the recruitment and function of osteoclasts after being released in the marrow compartment osteocytes produces clerostin which negatively interacts Wnt signalling and therefore inhibits bone formation. Osteocytes also produce DKK which targets the Wnt signaling pathway to control bone formation negatively.

15. MYOGENIC PRECURSOR MARKERS Myogenesis is the generation of muscle tissue when committed muscle stem cells or myoblasts proliferate into multinucleate into myotubes in the embryo. In Adult tissue , muscle- derived stem cells are distinct population of cells from muscle satellite cells which promote muscle stem cell regeneration to injury and disease. A cocktail of the myogenic marker CD56, the endothelial cell marker UAE-1 receptor and the perivascular cell marker CD146can be used to mark the myogenic precursor markers. ABCG2 and M- Cadherin-15/ M- Cadherin, Caveolin -1, CD34 are some myogenic precursor markers

16. MESENCHYMAL STEM CELL MARKERS Mesenchymal stem cell markers are multipotent mesoderm-derived progenitor cells with the capacity to differentiate into adipose, bone, cartilage and muscle tissues providing wide-ranging therapeutic avenues. Adult mesenchymal stem cells can be isolated from a stroma of the bone marrow. MSCs express a panel of key markers including markers CD10, CD13, CD73,CD105 and CD271. MSC derived from bone marrow ( BMMSCs) express a postnatal stem cells capable of self-renewing and differentiating into osteoblasts, chondrocytes, adipocytes and neural cells.

17. NEURAL STEM CELL MARKERS Neural stem cells are unique cells endowed with self-renewing, multipotent, responsible for the generation the main phenotypes of the nervous system. NSCs have the unique potential to produce clonally related progeny that upon differentiation ,constitute the central nervous system developed by neurons progeny that upon differentiation developed by neurons, astrocytes, oligodendrocytes , and the ependymal cells. Many neural cell types were identified and isolated by using cell surface marker expression. CD133 is expressed on the surface of Neural stem cell and has ben widely used to isolate Neural stem cell from human brain. CD15, a stage -specific embryonic antigenic-1 is now identified as a marker of Neural stem cell and radial glia from the subventricular zone(SVZ) in mice.

18. SKIN STEM CELL MARKERS Multipotent skin stem cells or epidermal stem cells are responsible for tissue homeostasis during normal cell turnover and wound healing. Such skin stem cells were found to reside within a niche within the hair follicle. Although , predominantly under quiescence or a slow cell cycle, epidermal stem cells can be stimulated to proliferate and differentiate into the specialized cells that composed a hair follicle during wound healing. K15 protein expression not only marks on epidermal stem or progenitor cell subpopulation and also represents basal-like cells during the epidermal differentiation program. Some integrins have been suggested as markers for epidermal stem cells. The ᾳ₆ᵦ₄ integrin associated with and ᾳ ₃ ᵦ ₁ integrins associated with the lateral ( mainly) and basal (minor) surfaces of epidermal basal cells.

19. INTESTINAL STEM CELL MARKERS It is now widely recognized that multipotent intestinal stem cells that reside between villi within the crypts drive continuous replenishment of the epithelial cells. Intestinal stem cells or crypt cells have the ability to self-renew and regenerate the intestinal tissue by differentiating into various intestinal cells including endocrine cells, enterocytes, goblet cells, and Paneth cells. Wang et al demonstrate that Lrig1 is implicated in maintaining the intestinal epithelial homeostasis and marks stem cells in the intestine . Lgr5 is used as a stem cell marker of the intestinal epithelium and the hair follicle however, intestinal organoids can also develop from Lgr5- cells.

20. ADIPOSE- DERIVED STEM CELL MARKERS Adipose tissue is composed primarily of adipocytes, cells that function to store energy in the form of lipids droplets. Additionally, pluripotent progenitor cells called adipose tissue by the expression of markers such as Integrin family members, CD44 and ICAM-1/CD54. Like mesenchymal stem cells, Multipotent adipose derived stem cells have been shown to differentiate into cells of the mesodermal lineage including adipocytes, chondrocytes, osteoblasts, osteoclasts and myoblasts in vitro. 2. Adipose- derived stem cell markers express characteristics adhesion and receptor molecules ,surface enzymes, extracellular matrix and cytoskeleton proteins associated with the stromal cell phenotype of ASCs resembles that of bone marrow derived mesenchymal stem cells or stomal cells (MSCs) and skeletal muscle- derived cells. Some of the adipose derived stem cell markers are:- CD13, CD29 , CD 44, CD71 , CD71 , CD90 , CD105/SH2 and SH3 surface markers

21. OVARY AND TUBAL STEM CELL MARKERS Lgr5 is a stem cell marker for multiple epithelia , and has recently been shown to the marker of stem/ progenitor cells in the ovary and tubal epithelia. Various Ovarian cancer stem cell markers such as ALDH1,CD44, AND CD117, ALDH1 is an enzyme involved in the metabolism of retinoic acids and probably plays a central role in differentiation ALDH1 is also involved in cell surface glycoprotein involved in invasion and metastasis via the activation of thePI3K/AKT pathway. CD117 is a protooncogene (c-kit) that encodes for a tyrosine kinase receptor and plays an important role in oncogenic process such as cell proliferation and tumor development. An ovarian serous carcinogenic sequence was recently described and it has been suggested that most high-grade serous ovarian cancers( HGSC) would have a tubal origin and a tubal precursor lesion called “serous tubal intraepithelial carcinomas (STICs)

22. ECTODERM AND ENDODERM MARKERS E ctoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm (middle layer) and endoderm (most proximal layer), with the ectoderm as the most exterior (or distal) layer. Certain factors mark the ectoderm including Otx2, Chordin, p63/TP73L, FGF-8, Pax2. FoxJ3, Pax6, GBX2, SOX1, Nestin, beta- Tubulin, and Noggin. Endoderm formation depends on two sequential positive feedback loops mediated by Cripto and Bmp4/Wnt3 that are activated by mature or uncleaved Nodal, respectively, to sustain Nodal signaling from implantation throughout gastrulation ENDM1 and Flk1 have been used as a definitive mouse endodermal cell marker and a mesoderm cell marker, respectively 

23. CYTOKERATIN MARKERS Cytokeratin markers are the intermediate filaments can serve as a marker system epithelial cells at different stages of cellular differentiation. The expression of these cytokeratins relies on the type of epithelium and their expression also changes during the course of normal epithelial cell differentiation. Cytokeratin markers can provide valuable supporting evidence in combination with a standard marker to subfractionate populations of stem, progenitor and differentiated cells. One of the most well-characterized cytokeratin expression patterns is available in skin, where CK15 expression is restricted to the bulge region multipotent stem cells, but replaced by CK5 As differentiation proceeds, CK5 is replaced by CK10 and eventually the terminal differentiation marker involucrin . Now it is understood that CK14 and CK5 are expressed in urothelial basal cells, CK8 and CK18 mark intermediate cells and CK20 are expressed only in terminally differentiated umbrella cells

24. REFERENCES Pazhanisamy, Senthil. “Stem Cell Markers.”  Materials and Methods , vol. MATER METHODS 2013;3:200, 7 Mar. 2020, www.labome.com/method/Stem-Cell-Markers.html . Zhao, Wenxiu, et al. “Embryonic Stem Cell Markers.”  Molecules , vol. 17, no. 6, 25 May 2012, pp. 6196–6236, 10.3390/molecules17066196. Accessed 1 Mar. 2020.