Embryonic Stem Cell Markers

Embryonic stem cells are characterized by their ability to propagate indefinitely in culture, maintaining a normal karyotype and their undifferentiated state. They are undifferentiated pluripotent cells and have the potential of differentiating into any specialized cell type in the body.

MDS offers services for characterizing embryonal stem (ES) cells, and lineage- or tissue-specific neonatally derived stem cells from a human as well as a variety of species with regard to germline chimerism, marker expression, differentiative potential, transfectability, selective agent sensitivity and vector suitability and gene targeting vectors

• Stella
• Cytokines
• Secretory markers
• Surface Molecules

• Stella
  Stella is a gene specifically expressed in primordial germ cells, oocytes, preimplantation embryos, and pluripotent cells. It encodes a protein with a SAP-like domain and a splicing factor motif-like structure, suggesting possible roles in chromosomal organization or RNA processing. Stella-deficient females displayed severely reduced fertility due to a lack of maternally inherited Stella-protein in their oocytes. Embryos without Stella are compromised in preimplantation development and rarely reach the blastocyst stage. Stella is thus one of few known mammalian maternal effect genes.
  Alternative names for Stella - Primordial Germ Cell Marker
  • Compaction-associated protein 1
  • Developmental pluripotency-associated protein 3
  • Dppa3
  • PGC7
  • Stella-related protein
  • Stellar
  
  
• Cytokines
  • Gremlin 1
    In Xenopus, Gremlin 1 belongs to a novel gene family that acts as BMP antagonists in embryonic explants. The human homolog of Gremlin 1 (CKTFS1B1) is localized on human chromosome 15q13--> q15. Gremlin 1-specific mRNA is expressed in different human tissues, including brain, ovary, intestine and colon. It has been suggested that down-regulation of Gremlin 1 is associated with tumor progression and supports the hypothesis that human Gremlin 1 may play an important role during both neuroembryological development and carcinogenesis.
    Alternative names for Gremlin 1:
    • CKTSF1B1
    • Cysteine knot superfamily BMP antagonist 1
    • DAND2
    • DRM
    • IHG2
    • PIG2
    • Proliferation-inducing gene 2 protein
    
    
  • IRF6
    Interferon regulatory factor 6 (IRF6) belongs to a family of 9 transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. This domain, called SMIR (for SMAD IRF-binding domain), is also found in IRF3 and IRF7. Other interferon regulatory factors include IRF1 on 5q, IRF2 on 4q, IRF3 on 19q, and IRF4 on 6p. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection. Mutation in the IRF6 gene can cause van der Woude syndrome and popliteal pterygium syndrome. VWS is an autosomal dominant form of cleft lip and palate associated with lip pits, and is the most common syndromic form of cleft lip or palate. PPS is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies.
    Alternative names for IRF6:
    • Interferon regulatory factor 6
    • LPS
    • OFC 6
    • OFC6
    • PIT
    • PPS
    • VWS
  
  
• Secretory markers
  • Cripto
    The cripto gene is expressed both in ES cells and during the early phases of embryo development while in adults it is reactivated in a wide range of epithelial cancers.
    
    
  • FGF10
    FGF10 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, and tumor growth and invasion. This protein exhibits mitogenic activity for keratinizing epidermal cells but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. This gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis and initiation of limb bud formation. This gene is also implicated to be a primary factor in the process of wound healing.
    
    
  • GDF3 (Growth differentiation factor 3)
    GDF3 is a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site that is cleaved to produce a mature protein containing seven conserved cysteine residues. The members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. The function of this protein is unknown but expression studies suggest it may be involved in regulation of the adult lymphatic and erythroid systems and embryonic development
  
  
• Surface Molecules
  
  • CD9
    CD9 antigen is a glycoprotein expressed on the surface of developing B lymphocytes, platelets, monocytes, eosinophils, basophils, stimulated T lymphocytes and by neurons and glial cells in the peripheral nervous system. It belongs to a family of membrane proteins termed tetraspanins that transverse the membrane four times. In pre-B cells and platelets, CD9 antigen regulates cell activation and aggregation possibly through an association with the integrin CD41 / CD61 (GPIIb / GPIIIa). It also regulates cell motility in a variety of cell lines and appears to be an important regulator of Schwann cell behavior in peripheral nerves.
    
    
  • Delta 1
    Delta 1 is a mouse homolog of the Notch Delta ligand and acts as a ligand for Notch receptors. Delta 1 is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication. Delta 1 blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor.
    
    
  • Integrin alpha 6
    Integrins are important extracellular matrix (ECM) receptor proteins located on cell surfaces. They are heterodimers composed of an alpha and a beta transmembrane glycoprotein subunit. Around twenty-two different integrins (different alpha / beta subunit combinations) are found in nature. Integrins are generally present in high concentrations at the cell surface, but, unlike most other cell surface receptors, they bind ligands with very low affinity. Due to their weak individual binding, integrins need to cluster and bind in groups in order to effectively bind the ECM. Integrins bind many different ligands including laminin. Each integrin is made up of a large N terminal extracellular domain that binds the ECM ligand and a small C terminal cytoplasmic domain that mediates interaction with the actin cytoskeleton and signaling function. Integrin alpha 6 complexes are receptors for laminins, which are components of basement membranes. Integrin alpha 6 complexes may play an important role in embryogenesis.
    
    
  • Integrin beta 1
    Integrin beta 1, also known as CD29, is a 130 kDa transmembrane glycoprotein that forms non-covalent complexes with various Integrin alpha subunits (including alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, and alpha 6, also known, respectively, as CD49a, CD49b, CD49c, CD49d, CD49e, and CD49f) to form the functional receptors that bind to specific extracellular matrix proteins. Integrin receptors are involved in the regulation of a variety of important biological functions, including embryonic development, wound repair, hemostasis, and prevention of programmed cell death. They are also implicated in abnormal pathological states such as tumor directed angiogenesis, tumor cell growth, and metastasis. These heterodimeric receptors bridge the cytoplasmic actin cytoskeleton with proteins present in the extracellular matrix and/or on adjacent cells. The clustering of integrins on a cell surface leads to the formation of focal contacts. Interactions between integrins and the extracellular matrix lead to activation of signal transduction pathways and regulation of gene expression.
    
    
  • Sonic Hedgehog
    Sonic Hedgehog, which is expressed only during embryogenesis, is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the Sonic Hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signaling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signaling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. In addition, it is thought that mutations in this gene or in its signaling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities.
    
    
  • Sonic hedgehog homolog (SHH)
    SHH is one of three proteins in the mammalian hedgehog family, the others being desert hedgehog (DHH) and Indian hedgehog (IHH). SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example of a morphogen as defined by Lewis Wolpert's French flag model - a molecule that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration. SHH remains important in the adult. It controls cell division of adult stem cells and has been implicated in development of some cancers.
    
    
  • SSEA-1
    SSEA-1 is a lactoseries oligosaccharide antigen that is expressed on the surface of murine embryonal carcinoma and embryonic stem cells, early mouse embryos, murine and human germ cells. It is not found on undifferentiated human embryonal carcinoma and embryonic stem cells, but its expression increases on differentiation of these cell types. In contrast, in mice SSEA1 expression on embryonic stem and embryonal carcinoma cells decreases as these cell types differentiate.
    
    
  • SSEA3
    SSEA3 is a globoseries carbohydrate antigen present on both cell surface glycolipids and glycopeptides. It is found on the surface of mouse oocytes, becoming restricted to the intracellular mass of the early blastocyst and then to the primitive endoderm. It is present on the surface of human teratocarcinoma cells (EC), embryonic germ cells (EG) and embryonic stem cells (ES) but not mouse undifferentiated mouse cells of these types. SSEA3 expression decreases as human EC, ES and EG cells differentiate but increases on differentiation of mouse EC, ES and EG cells. It is also found on the surface of mouse erythrocytes.
    
    
  • SSEA4
    SSEA4 (Stage-specific embryonic antigen 4) is a glycoprotein expressed early in embryonic development and in pluripotent stem cells. SSEA-4 can be used as a marker of Human Embryonic Stem Cells, Human Embryonic Carcinoma Cells and Human Embryonic Germ Cells. Monoclonal antibodies to this target have been widely used in the characterization of pluripotent stem cells. Mouse pluripotent stem cells are not recognized by anti-SSEA-4 antibodies but do express the antigen upon differentiation.
    
    
  • TRA-1-60
    TRA-1-60 is a marker of Human Embryonic Stem, Germ and Carcinoma Cells but not Mouse Embryonic Stem, Germ or Carcinoma Cells. The core protein recognized by TRA-1-60 has not been identified but the antibody is thought to recognize carbohydrate epitopes associated with a high molecular weight proteoglycan. The TRA antibodies are named after the Battle of Trafalgar; TRA does not stand for "Tumor Rejection Antigen" as is believed by some.