Best Stem Cell Markers

My trip to Stanford and LA for the Stem Cell training was very informative and helpful.
Here are some of the key things I learned on this trip.
1. Recently there was an international conference on stem cell us in ocular surface disease. The group of experts agreed on could definitively state which are the key markers to prove “stemness.” Still the classic markers, such as CD34+; Hematopoietic stem cell (CD45+ CD34lo); Adipose derived stromal stem cell (CD45- CD34+) are generally agreed upon. 
2. Stem cells can be determined if the donor is female and recipient is male by looking for the Y chromosome.

3. Flow cytometry is a way to generally isolate stem cells but it is not perfect.

Stem cell marker

From Wikipedia, the free encyclopedia
Stem cell markers are genes and their protein products used by scientists to isolate and identify stem cells. Stem cells can also be identified by functional assays. Below is a list of genes/protein products that can be used to identify various types of stem cells, or functional assays that do the same.[1] The initial version of the list below was obtained by mining the PubMed database as described in [2]

Stem cell marker names[edit]


  1. Jump up^ “Appendix E: Stem Cell Markers”Stem Cell InformationBethesda, MarylandNational Institutes of Health. 17 June 2001. Retrieved 23 July 2009.
  2. Jump up^ Trifan M, Perez-Iratxeta C, Andrade-Navarro MA, Ionescu D (July 13–16, 2009). “Text Mining and Semantic Search with a Predicate Argument Structure Database”International Conference on Bioinformatics & Computational Biology, BIOCOMP 2009, Las Vegas Nevada, USA, 2 Volumes.
  3. Jump up^ Petrenko O, Beavis A, Klaine M, Kittappa R, Godin I, Lemischka IR (June 1999). “The molecular characterization of the fetal stem cell marker AA4”. Immunity10 (6): 691–700. doi:10.1016/S1074-7613(00)80068-0PMID 10403644.
  4. Jump up to:a b Taoudi S, Morrison AM, Inoue H, Gribi R, Ure J, Medvinsky A (September 2005). “Progressive divergence of definitive haematopoietic stem cells from the endothelial compartment does not depend on contact with the foetal liver”. Development132(18): 4179–91. doi:10.1242/dev.01974PMID 16107475.
  5. Jump up^ Islam MO, Kanemura Y, Tajria J, et al. (July 2005). “Characterization of ABC transporter ABCB1 expressed in human neural stem/progenitor cells”. FEBS Letters579 (17): 3473–80. doi:10.1016/j.febslet.2005.05.019PMID 15950972.
  6. Jump up^ Frank NY, Margaryan A, Huang Y, et al. (May 2005). “ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma”. Cancer Research65 (10): 4320–33. doi:10.1158/0008-5472.CAN-04-3327PMID 15899824.
  7. Jump up to:a b Bernardo AS, Barrow J, Hay CW, et al. (July 2006). “Presence of endocrine and exocrine markers in EGFP-positive cells from the developing pancreas of a nestin/EGFP mouse”. Molecular and Cellular Endocrinology253 (1–2): 14–21. doi:10.1016/j.mce.2006.03.003PMID 16698177.
  8. Jump up^ Chute JP, Muramoto GG, Whitesides J, et al. (August 2006). “Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells”Proceedings of the National Academy of Sciences of the United States of America103 (31): 11707–12. doi:10.1073/pnas.0603806103PMC 1544234Freely accessiblePMID 16857736.
  9. Jump up^ Nagafuchi S, Katsuta H, Kogawa K, et al. (July 1999). “Establishment of an embryonic stem (ES) cell line derived from a non-obese diabetic (NOD) mouse: in vivo differentiation into lymphocytes and potential for germ line transmission”. FEBS Letters455 (1–2): 101–4. doi:10.1016/S0014-5793(99)00801-7PMID 10428481.
  10. Jump up to:a b Shinohara T, Avarbock MR, Brinster RL (May 1999). “β1- and α6-integrin are surface markers on mouse spermatogonial stem cells”Proceedings of the National Academy of Sciences of the United States of America96 (10): 5504–9. doi:10.1073/pnas.96.10.5504PMC 21889Freely accessiblePMID 10318913.
  11. Jump up^ Katoh M (December 2005). “WNT2B: comparative integromics and clinical applications (Review)”. International Journal of Molecular Medicine16 (6): 1103–8. doi:10.3892/ijmm.16.6.1103PMID 16273293.
  12. Jump up to:a b Gordon B, Haire W, Ruby E, et al. (March 1997). “Factors predicting morbidity following hematopoietic stem cell transplantation”. Bone Marrow Transplantation19 (5): 497–501. doi:10.1038/sj.bmt.1700684PMID 9052918.
  13. Jump up^ Harris MT, Schwarting GA, Stout RD (September 1981). “Selective expression of asialo GM1 on maturational subsets of lymphocytes in normal and athymic mice”. Thymus3 (3): 153–67. PMID 6171918.
  14. Jump up^ Polakowska RR, Piacentini M, Bartlett R, Goldsmith LA, Haake AR (March 1994). “Apoptosis in human skin development: morphogenesis, periderm, and stem cells”. Developmental Dynamics199 (3): 176–88. doi:10.1002/aja.1001990303PMID 7517223.
  15. Jump up^ Asari S, Okada S, Ohkubo Y, et al. (August 2004). “Beta-galactosidase of ROSA26 mice is a useful marker for detecting the definitive erythropoiesis after stem cell transplantation”. Transplantation78 (4): 516–23. doi:10.1097/01.TP.0000128854.20831.6FPMID 15446309.
  16. Jump up to:a b c d e Valente T, Junyent F, Auladell C (June 2005). “Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: differential phenotype of the Zac1-expressing cells during development”. Developmental Dynamics233 (2): 667–79. doi:10.1002/dvdy.20373PMID 15844099.
  17. Jump up^ Raisky O, Nykänen AI, Krebs R, et al. (April 2007). “VEGFR-1 and -2 regulate inflammation, myocardial angiogenesis, and arteriosclerosis in chronically rejecting cardiac allografts”. Arteriosclerosis, Thrombosis, and Vascular Biology27 (4): 819–25. doi:10.1161/01.ATV.0000260001.55955.6cPMID 17290032.
  18. Jump up^ Suzuki A, Zheng YW, Fukao K, Nakauchi H, Taniguchi H (2004). “Liver repopulation by c-Met-positive stem/progenitor cells isolated from the developing rat liver”. Hepato-gastroenterology51 (56): 423–6. PMID 15086173.
  19. Jump up^ Danet GH, Luongo JL, Butler G, et al. (August 2002). “C1qRp defines a new human stem cell population with hematopoietic and hepatic potential”Proceedings of the National Academy of Sciences of the United States of America99 (16): 10441–5. doi:10.1073/pnas.162104799PMC 124933Freely accessiblePMID 12140365.
  20. Jump up to:a b Nagatomo K, Komaki M, Sekiya I, et al. (August 2006). “Stem cell properties of human periodontal ligament cells”. Journal of Periodontal Research41 (4): 303–10. doi:10.1111/j.1600-0765.2006.00870.xPMID 16827724.
  21. Jump up^ Peichev M, Naiyer AJ, Pereira D, et al. (1 February 2000). “Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors”Blood95 (3): 952–8. PMID 10648408.
  22. Jump up^ Zhou L, Wei X, Cheng L, Tian J, Jiang JJ (March 2007). “CD133, one of the markers of cancer stem cells in Hep-2 cell line”. The Laryngoscope117 (3): 455–60. doi:10.1097/01.mlg.0000251586.15299.35PMID 17334305.
  23. Jump up^ Kania G, Corbeil D, Fuchs J, et al. (2005). “Somatic stem cell marker prominin-1/CD133 is expressed in embryonic stem cell-derived progenitors”. Stem Cells23 (6): 791–804. doi:10.1634/stemcells.2004-0232PMID 15917475.
  24. Jump up to:a b c d Herrera MB, Bruno S, Buttiglieri S, et al. (December 2006). “Isolation and characterization of a stem cell population from adult human liver”. Stem Cells24 (12): 2840–50. doi:10.1634/stemcells.2006-0114PMID 16945998.
  25. Jump up^ Pera MF, Herszfeld D (1998). “Differentiation of human pluripotent teratocarcinoma stem cells induced by bone morphogenetic protein-2”. Reproduction, Fertility, and Development10 (7–8): 551–5. doi:10.1071/RD98097PMID 10612460.
  26. Jump up^ Miranville A, Heeschen C, Sengenès C, Curat CA, Busse R, Bouloumié A (July 2004). “Improvement of postnatal neovascularization by human adipose tissue-derived stem cells”. Circulation110 (3): 349–55. doi:10.1161/01.CIR.0000135466.16823.D0PMID 15238461.
  27. Jump up^ Blakolmer K, Jaskiewicz K, Dunsford HA, Robson SC (June 1995). “Hematopoietic stem cell markers are expressed by ductal plate and bile duct cells in developing human liver”. Hepatology21 (6): 1510–6. doi:10.1002/hep.1840210606PMID 7539394.
  28. Jump up^ Ning H, Lin G, Lue TF, Lin CS (December 2006). “Neuron-like differentiation of adipose tissue-derived stromal cells and vascular smooth muscle cells”. Differentiation74 (9–10): 510–8. doi:10.1111/j.1432-0436.2006.00081.xPMID 17177848.
  29. Jump up^ Van Den Heuvel MC, Slooff MJ, Visser L, et al. (June 2001). “Expression of anti-OV6 antibody and anti-N-CAM antibody along the biliary line of normal and diseased human livers”. Hepatology33 (6): 1387–93. doi:10.1053/jhep.2001.24453PMID 11391527.
  30. Jump up^ Kanatsu-Shinohara M, Toyokuni S, Shinohara T (January 2004). “CD9 is a surface marker on mouse and rat male germline stem cells”. Biology of Reproduction70 (1): 70–5. doi:10.1095/biolreprod.103.020867PMID 12954725.
  31. Jump up^ Okumoto K, Saito T, Hattori E, et al. (May 2003). “Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation”. Biochemical and Biophysical Research Communications304 (4): 691–5. doi:10.1016/S0006-291X(03)00637-5PMID 12727209.
  32. Jump up^ Kimura H, Morii E, Ikeda JI, et al. (September 2006). “Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells”. Leukemia20 (9): 1551–6. doi:10.1038/sj.leu.2404312PMID 16926850.
  33. Jump up to:a b Regauer S (May 2006). “Extramammary Paget’s disease–a proliferation of adnexal origin?”. Histopathology48 (6): 723–9. doi:10.1111/j.1365-2559.2006.02405.xPMID 16681689.
  34. Jump up^ Schoof H, Lenhard M, Haecker A, Mayer KF, Jürgens G, Laux T (March 2000). “The stem cell population of Arabidopsis shoot meristems in maintained by a regulatory loop between the CLAVATA and WUSCHEL genes”. Cell100 (6): 635–44. doi:10.1016/S0092-8674(00)80700-XPMID 10761929.
  35. Jump up^ Scavennec J, Carcassonne Y, Gastaut JA, Blanc A, Cailla HL (1 August 1981). “Relationship between the levels of cyclic cytidine 3′:5′-monophosphate, cyclic guanosine 3′:5′-monophosphate, and cyclic adenosine 3′:5′-monophosphate in urines and leukocytes and the type of human leukemias”Cancer Research41 (8): 3222–7. PMID 6265079.
  36. Jump up^ Boulter CA, Wagner EF (March 1988). “The effects of v-src expression on the differentiation of embryonal carcinoma cells”. Oncogene2 (3): 207–14. PMID 3127777.
  37. Jump up to:a b c Giuliano CJ, Kerley-Hamilton JS, Bee T, et al. (October 2005). “Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity”. Biochimica et Biophysica Acta1731 (1): 48–56. doi:10.1016/j.bbaexp.2005.08.006PMID 16168501.
  38. Jump up^ Reid CD (June 1987). “The significance of endogenous erythroid colonies (EEC) in haematological disorders”. Blood Reviews1 (2): 133–40. doi:10.1016/0268-960X(87)90008-7PMID 3332094.
  39. Jump up^ Lane MA, Chen AC, Roman SD, Derguini F, Gudas LJ (November 1999). “Removal of LIF (leukemia inhibitory factor) results in increased vitamin A (retinol) metabolism to 4-oxoretinol in embryonic stem cells”Proceedings of the National Academy of Sciences of the United States of America96 (23): 13524–9. doi:10.1073/pnas.96.23.13524PMC 23981Freely accessiblePMID 10557354.
  40. Jump up^ Christensen JL, Weissman IL (December 2001). “Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells”Proceedings of the National Academy of Sciences of the United States of America98 (25): 14541–6. doi:10.1073/pnas.261562798PMC 64718Freely accessiblePMID 11724967.
  41. Jump up^ Hu Y, Zhang Z, Torsney E, et al. (May 2004). “Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice”The Journal of Clinical Investigation113 (9): 1258–65. doi:10.1172/JCI19628PMC 398426Freely accessiblePMID 15124016.
  42. Jump up to:a b c Anzai H, Nagayoshi M, Obata M, Ikawa Y, Atsumi T (February 1999). “Self-renewal and differentiation of a basic fibroblast growth factor-dependent multipotent hematopoietic cell line derived from embryonic stem cells”. Development, Growth & Differentiation41 (1): 51–8. doi:10.1046/j.1440-169x.1999.00412.xPMID 10445502.
  43. Jump up^ Rappold I, Ziegler BL, Köhler I, et al. (15 July 1997). “Functional and phenotypic characterization of cord blood and bone marrow subsets expressing FLT3 (CD135) receptor tyrosine kinase”. Blood90 (1): 111–25. PMID 9207445.
  44. Jump up^ Pfeilstöcker M, Karlic H, Paukovits J, et al. (April 1999). “In vivo and in vitro effects of cytokines and the hemoregulatory peptide dimer (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 on G alpha16-positive hematopoiesis”. Leukemia13 (4): 590–4. doi:10.1038/sj/leu/2401377PMID 10214866.
  45. Jump up^ Kume A, Hashiyama M, Suda T, Ozawa K (1999). “Green fluorescent protein as a selectable marker of retrovirally transduced hematopoietic progenitors”. Stem Cells17 (4): 226–32. doi:10.1002/stem.170226PMID 10437986.
  46. Jump up^ Sonoda T, Hayashi C, Seike H, et al. (February 1985). “Extensive proliferation of subsequently injected marrow cells in parental-to-F1 hematopoietic chimeras that restored normal stem cell concentration after initial transplantation”. Experimental Hematology13 (2): 143–50. PMID 2857651.
  47. Jump up to:a b c Perron M, Boy S, Amato MA, et al. (April 2003). “A novel function for Hedgehog signalling in retinal pigment epithelium differentiation”. Development130 (8): 1565–77. doi:10.1242/dev.00391PMID 12620982.
  48. Jump up^ Tschöpe D, Langer E, Schauseil S, Rösen P, Kaufmann L, Gries FA (February 1989). “Increased platelet volume–sign of impaired thrombopoiesis in diabetes mellitus”. Klinische Wochenschrift67(4): 253–9. doi:10.1007/BF01717328PMID 2927060.
  49. Jump up^ Czerwinski M, Kiem HP, Slattery JT (March 1997). “Human CD34+ cells do not express glutathione S-transferases alpha”. Gene Therapy4 (3): 268–70. doi:10.1038/ 9135742.
  50. Jump up^ Grskovic B, Pollaschek C, Mueller MM, Stuhlmeier KM (June 2006). “Expression of hyaluronan synthase genes in umbilical cord blood stem/progenitor cells”. Biochimica et Biophysica Acta1760 (6): 890–5. doi:10.1016/j.bbagen.2006.02.002PMID 16564133.
  51. Jump up^ Chapouton P, Adolf B, Leucht C, et al. (November 2006). “her5 expression reveals a pool of neural stem cells in the adult zebrafish midbrain”. Development133 (21): 4293–303. doi:10.1242/dev.02573PMID 17038515.
  52. Jump up^ Wang Q, Li N, Wang X, et al. (January 2007). “Membrane protein hMYADM preferentially expressed in myeloid cells is up-regulated during differentiation of stem cells and myeloid leukemia cells”. Life Sciences80 (5): 420–9. doi:10.1016/j.lfs.2006.09.043PMID 17097684.
  53. Jump up^ Stahl J, Wobus AM, Ihrig S, Lutsch G, Bielka H (September 1992). “The small heat shock protein hsp25 is accumulated in P19 embryonal carcinoma cells and embryonic stem cells of line BLC6 during differentiation”. Differentiation51 (1): 33–7. doi:10.1111/j.1432-0436.1992.tb00677.xPMID 1451960.
  54. Jump up^ Gultice AD, Selesniemi KL, Brown TL (June 2006). “Hypoxia inhibits differentiation of lineage-specific Rcho-1 trophoblast giant cells”. Biology of Reproduction74 (6): 1041–50. doi:10.1095/biolreprod.105.047845PMID 16481593.
  55. Jump up^ Testa U, Riccioni R, Diverio D, Rossini A, Lo Coco F, Peschle C (February 2004). “Interleukin-3 receptor in acute leukemia”. Leukemia18 (2): 219–26. doi:10.1038/sj.leu.2403224PMID 14671644.
  56. Jump up^ Hall PE, Lathia JD, Miller NG, Caldwell MA, ffrench-Constant C (September 2006). “Integrins are markers of human neural stem cells”. Stem Cells24 (9): 2078–84. doi:10.1634/stemcells.2005-0595PMID 16690778.
  57. Jump up^ Jordan CT, Upchurch D, Szilvassy SJ, et al. (October 2000). “The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells”. Leukemia14(10): 1777–84. doi:10.1038/sj.leu.2401903PMID 11021753.
  58. Jump up^ Jendelová P, Herynek V, Urdzíková L, et al. (April 2004). “Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord”. Journal of Neuroscience Research76 (2): 232–43. doi:10.1002/jnr.20041PMID 15048921.
  59. Jump up^ Ziegler BL, Valtieri M, Porada GA, et al. (September 1999). “KDR receptor: a key marker defining hematopoietic stem cells”. Science285 (5433): 1553–8. doi:10.1126/science.285.5433.1553PMID 10477517.
  60. Jump up^ Misago N, Narisawa Y (September 2006). “Cytokeratin 15 expression in neoplasms with sebaceous differentiation”. Journal of Cutaneous Pathology33 (9): 634–41. doi:10.1111/j.1600-0560.2006.00500.xPMID 16965339.
  61. Jump up^ Tiede S, Koop N, Kloepper JE, Fässler R, Paus R (November 2009). “Nonviral in situ green fluorescent protein labeling and culture of primary, adult human hair follicle epithelial progenitor cells”. Stem Cells27 (11): 2793–803. doi:10.1002/stem.213PMID 19750535.
  62. Jump up^ Nijhof JG, Braun KM, Giangreco A, et al. (August 2006). “The cell-surface marker MTS24 identifies a novel population of follicular keratinocytes with characteristics of progenitor cells”. Development133 (15): 3027–37. doi:10.1242/dev.02443PMID 16818453.
  63. Jump up^ Youn SW, Kim DS, Cho HJ, et al. (August 2004). “Cellular senescence induced loss of stem cell proportion in the skin in vitro”. Journal of Dermatological Science35 (2): 113–23. doi:10.1016/j.jdermsci.2004.04.002PMID 15265523.
  64. Jump up^ Fu XB, Sun TZ, Li XK, Sheng ZY (February 2005). “Morphological and distribution characteristics of sweat glands in hypertrophic scar and their possible effects on sweat gland regeneration”Chinese Medical Journal118 (3): 186–91. PMID 15740645.
  65. Jump up to:a b Clarke RB (December 2005). “Isolation and characterization of human mammary stem cells”. Cell Proliferation38 (6): 375–86. doi:10.1111/j.1365-2184.2005.00357.xPMID 16300651.
  66. Jump up^ Perry SS, Wang H, Pierce LJ, Yang AM, Tsai S, Spangrude GJ (April 2004). “L-selectin defines a bone marrow analog to the thymic early T-lineage progenitor”. Blood103 (8): 2990–6. doi:10.1182/blood-2003-09-3030PMID 15070675.
  67. Jump up^ Constantinescu D, Gray HL, Sammak PJ, Schatten GP, Csoka AB (January 2006). “Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation”. Stem Cells24(1): 177–85. doi:10.1634/stemcells.2004-0159PMID 16179429.
  68. Jump up^ Muramatsu T, Muramatsu H (2004). “Carbohydrate antigens expressed on stem cells and early embryonic cells”. Glycoconjugate Journal21 (1–2): 41–5. doi:10.1023/B:GLYC.0000043746.77504.28PMID 15467397.
  69. Jump up^ Ganat YM, Silbereis J, Cave C, et al. (August 2006). “Early postnatal astroglial cells produce multilineage precursors and neural stem cells in vivo”. The Journal of Neuroscience26 (33): 8609–21. doi:10.1523/JNEUROSCI.2532-06.2006PMID 16914687.
  70. Jump up^ van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007). “Identification of stem cells in small intestine and colon by marker gene Lgr5”. Nature449 (7165): 1003–1007. doi:10.1038/nature06196PMID 17934449.
  71. Jump up^ Yamaguchi YL, Tanaka SS, Kasa M, Yasuda K, Tam PP, Matsui Y (August 2006). “Expression of low density lipoprotein receptor-related protein 4 (Lrp4) gene in the mouse germ cells”. Gene Expression Patterns6 (6): 607–12. doi:10.1016/j.modgep.2005.11.013PMID 16434236.
  72. Jump up^ Mohan A, Kandalam M, Ramkumar HL, Gopal L, Krishnakumar S (July 2006). “Stem cell markers: ABCG2 and MCM2 expression in retinoblastoma”The British Journal of Ophthalmology90(7): 889–93. doi:10.1136/bjo.2005.089219PMC 1857132Freely accessiblePMID 16556617.
  73. Jump up^ Legg J, Jensen UB, Broad S, Leigh I, Watt FM (December 2003). “Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in human interfollicular epidermis”. Development130 (24): 6049–63. doi:10.1242/dev.00837PMID 14573520.
  74. Jump up^ Donnelly ET, Bardwell H, Thomas GA, et al. (June 2005). “Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon”British Journal of Cancer92 (12): 2160–5. doi:10.1038/sj.bjc.6602633PMC 2361830Freely accessiblePMID 15928667.
  75. Jump up^ Hutter JJ, Hecht F, Kaiser-McCaw B, et al. (1984). “Bone marrow monosomy 7: hematologic and clinical manifestations in childhood and adolescence”. Hematological Oncology2 (1): 5–12. doi:10.1002/hon.2900020103PMID 6588021.
  76. Jump up^ Colombo E, Galli R, Cossu G, Gécz J, Broccoli V (November 2004). “Mouse orthologue of ARX, a gene mutated in several X-linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons”. Developmental Dynamics231 (3): 631–9. doi:10.1002/dvdy.20164PMID 15376319.
  77. Jump up^ Steinbach D, Wittig S, Cario G, et al. (December 2003). “The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype”. Blood102 (13): 4493–8. doi:10.1182/blood-2002-11-3461PMID 12816874.
  78. Jump up to:a b Clarke RB, Spence K, Anderson E, Howell A, Okano H, Potten CS (January 2005). “A putative human breast stem cell population is enriched for steroid receptor-positive cells”. Developmental Biology277 (2): 443–56. doi:10.1016/j.ydbio.2004.07.044PMID 15617686.
  79. Jump up^ Yoshida S, Shimmura S, Nagoshi N, et al. (December 2006). “Isolation of multipotent neural crest-derived stem cells from the adult mouse cornea”. Stem Cells24 (12): 2714–22. doi:10.1634/stemcells.2006-0156PMID 16888282.
  80. Jump up^ Staud F, Pavek P (April 2005). “Breast cancer resistance protein (BCRP/ABCG2)”. The International Journal of Biochemistry & Cell Biology37 (4): 720–5. doi:10.1016/j.biocel.2004.11.004PMID 15694832.
  81. Jump up^ Loo DT, Althoen MC, Cotman CW (October 1995). “Differentiation of serum-free mouse embryo cells into astrocytes is accompanied by induction of glutamine synthetase activity”. Journal of Neuroscience Research42 (2): 184–91. doi:10.1002/jnr.490420205PMID 8568918.
  82. Jump up^ Okawa H, Okuda O, Arai H, Sakuragawa N, Sato K (December 2001). “Amniotic epithelial cells transform into neuron-like cells in the ischemic brain”. NeuroReport12 (18): 4003–7. doi:10.1097/00001756-200112210-00030PMID 11742228.
  83. Jump up^ Neudenberger J, Hotfilder M, Rosemann A, et al. (May 2006). “Lack of expression of the chondroitin sulphate proteoglycan neuron-glial antigen 2 on candidate stem cell populations in paediatric acute myeloid leukaemia/abn(11q23) and acute lymphoblastic leukaemia/t(4;11)”. British Journal of Haematology133 (3): 337–44. doi:10.1111/j.1365-2141.2006.06013.xPMID 16643437.
  84. Jump up^ Umemoto T, Yamato M, Nishida K, et al. (December 2005). “Rat limbal epithelial side population cells exhibit a distinct expression of stem cell markers that are lacking in side population cells from the central cornea”. FEBS Letters579 (29): 6569–74. doi:10.1016/j.febslet.2005.10.047PMID 16297384.
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  86. Jump up^ Kafienah W, Mistry S, Williams C, Hollander AP (April 2006). “Nucleostemin is a marker of proliferating stromal stem cells in adult human bone marrow”. Stem Cells24 (4): 1113–20. doi:10.1634/stemcells.2005-0416PMID 16282439.
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Stem Cell Markers

First Printed in R&D Systems 2003 Catalog


While stem cells are best defined functionally, a number of molecular markers have been used to characterize various stem cell populations.
Although functions have yet to be ascertained for many of these early markers, their unique expression pattern and timing provide a useful tool for scientists to initially identify as well as isolate stem cells. This mini-review summarizes evidence regarding the roles of specific markers in defining embryonic, hematopoietic, mesenchymal/stromal, and neural stem cell populations. For most of the molecules discussed, studies performed both in vitro and in vivo support their significant role in characterizing stem cells. Until more is known about the novel marker-negative stem cell population, however, uncertainty still exists regarding the benefits of using these markers alone or in various combinations when identifying and isolating cells for stem cell research.

Embryonic Stem Cell Markers

Oct-4: Oct-4 (also termed Oct-3 or Oct-3/4), one of the POU transcription factors, was originally identified as a DNA-binding protein that activates gene transcription via a cis-element containing octamer motif.1 It is expressed in totipotent embryonic stem and germ cells.2, 3 A critical level of Oct-4 expression is required to sustain stem cell self-renewal and pluripotency.4 Differentiation of embryonic stem (ES) cells results in down- regulation of Oct-4, an event essential for a proper and divergent developmental program.5 Oct-4 is not only a master regulator of pluripotency that controls lineage commitment, but is also the first and most recognized marker used for the identification of totipotent ES cells.
SSEAs (Stage Specific Embryonic Antigens): SSEAs were originally identified by three monoclonal antibodies (Abs) recognizing defined carbohydrate epitopes associated with lacto- and globo-series glycolipids, SSEA-1, -3 and – 4.6 SSEA-1 is expressed on the surface of preimplantation-stage murine embryos (i.e. at the eight cell stage) and has been found on the surface of teratocarcinoma stem cells, but not on their differentiated derivatives.7, 8 The oviduct epithelium, endometrium and epididymis, as well as some areas of the brain and kidney tubules in adult mice have also been shown to be reactive with SSEA-1 Abs.9 SSEA-3 and -4 are synthesized during oogenesis and are present in the membranes of oocytes, zygotes and early cleavage-stage embryos.10, 11 Biological roles of these carbohydrate-associated molecules have been suggested in controlling cell surface interactions during development.6 Undifferentiated primate ES cells, human EC and ES cells express SSEA-3 and SSEA-4, but not SSEA-1. Undifferentiated mouse ES cells express SSEA-1, but not SSEA-3 or SSEA-4.12, 13

Hematopoietic Stem Cell Markers

Stem Cell Markers
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Figure 1. A structure model of CD133 proposed by Miraglia S. et al.30 This protein has an extracellular N-terminus, 5 hydrophobic transmembrane domains, 2 small cytoplasmic loops, 2 large extracellular loops and a cytoplasmic C-termus.

CD34: The cell surface sialomucin CD34 has been a focus of interest ever since it was found expressed on a small fraction of human bone marrow cells.14 The CD34+-enriched cell population from marrow or mobilized peripheral blood appears responsible for most of the hematopoietic activity.14, 15, 16, 17, 18, 19, 20, 21CD34 has therefore been considered to be the most critical marker for hematopoietic stem cells (HSCs). CD34 expression on primitive cells is down-regulated as they differentiate into mature cells.22 It is also found on clonogenic progenitors, however, and some lineage-committed cells.23 Although its precise function is still unknown, the pattern of expression of CD34 suggests that it plays a significant role in early hematopoiesis.22 The theory of CD34 being the most primitive HSC marker, however, has recently been challenged. Osawa et al. first demonstrated that murine HSCs could be CD34 negative.24 In addition, a low level of engraftment and hematopoietic capacity has been demonstrated in human CD34 cells.25 Transplantation studies also showed repopulating activity in a CD34 cell population in fetal sheep.26 Additionally, studies have shown that both murine and human CD34cells may be derived from CD34 cells.27, 28 Collectively, these reports suggest the possibility that HSCs may be CD34+ or CD34 and that selection of cells expressing CD34 might result in exclusion of more primitive stem cells. Nevertheless, almost all clinical and experimental protocols including ex vivo culture, gene therapy, and HSC transplantation are currently designed for cell populations enriched for CD34+ cells.

Stem Cell Markers
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Figure 2. The family of ABC transporters is characterized by the presence of an ATP-binding cassette region, which hydrolyzes ATP to support energy- dependent substrate exportation from the intracellular cytoplasm to the extracellular space. Full-length transporters contain two mirror image halves that are separated by a flexible linker region (not shown). Half-transporters, e.g. ABCG2, function as homo- or heterodimers and may be localized to the plasma membrane.

CD133: CD133, a 120 kDa, glycosylated protein containing five transmembrane domains (Figure 1), was identified initially by the AC133 monoclonal Ab, which recognizes a CD34+ subset of human HSCs.29, 30 A CD133 isoform, AC133-2, has been recently cloned and identified as the original surface antigen recognized by the AC133 Ab.31 CD133 may provide an alternative to CD34 for HSC selection and ex vivo expansion. A CD133+ enriched subset can be expanded in a similar manner as a CD34+ enriched subset, retaining its multilineage capacity.32 Recent studies have offered evidence that CD133 expression is not limited to primitive blood cells, but defines unique cell populations in non-hematopoietic tissues as well. CD133+ progenitor cells from peripheral blood can be induced to differentiate into endothelial cells in vitro.33 In addition, human neural stem cells can be directly isolated by using an anti-CD133 Ab.34
ABCG2: ABCG2 (ATP-binding cassette superfamily G member 2) is a determinant of the Hoechst-negative phenotype of side population (SP) cells and found in a wide variety of stem cells, including HSC.35, 36 ABCG2 is a member of the family of ABC transporters and was first identified in a breast cancer cell line.37 It belongs to the half-transporter group and is unique as it is localized to the plasma membrane (Figure 2).38 The expression of ABCG2 appears greatest on CD34cells and is down-regulated with the acquisition of CD34 on the cell surface.35 Down-regulation in ABCG2 expression is also observed in various committed hematopoietic progenitors.39 ABCG2 may therefore serve as a more promising marker than CD34 for primitive HSC isolation and characterization. The expression pattern of ABCG2, however, is not limited to HSC. ABCG2 expression exclusively characterizes the Hoechst SP phenotype in cells from diverse sources, including monkey bone marrow, mouse skeletal muscle and ES cells.35 The potential plasticity of SP cells has been demonstrated by studies showing that cardiomyocytes and muscle can be regenerated from transplanted bone marrow-derived SP cells.40, 41 Exclusive expression of ABCG2 on SP cells suggests that ABCG2 may be a potential marker for positive selection of pluripotent stem cells from various adult sources. ABCG2 has been implicated in playing a functional role in developmental stem cell biology (see reference 42 for a review).
Sca-1: Sca-1 (stem cell antigen 1, Ly-6A/E), an 18 kDa phosphatidylinositol-anchored protein, is a member of the Ly-6 antigen family.43 Sca-1 is the most recognized HSC marker in mice with both Ly-6 haplotypes as it is expressed on multipotent HSCs.44, 45 An anti-Sca-1 Ab is frequently used in combination with negative selection for expression of a number of cell surface markers characteristic of differentiated cells of hematolymphoid lineages (Lin) to identify and isolate murine HSCs. Sca-1+ HSCs can be found in the adult bone marrow, fetal liver and mobilized peripheral blood and spleen within the adult animal.44, 45, 46, 47, 48, 49Sca-1 has also been discovered in several non-hematopoietic tissues,43 however, and can be used to enrich progenitor cell populations other than HSCs.50 Sca-1 may be involved in regulating both B and T cell activation.51, 52, 53, 54

Mesenchymal/Stromal Stem Cell Markers

STRO-1: The murine IgM monoclonal Ab STRO-1, produced from an immunization with a population of human CD34+ bone marrow cells, can identify a cell surface antigen expressed by stromal elements in human bone marrow.55 From bone marrow cells, the frequency of fibroblast colony-forming cells (CFU-F) is enriched approximately 100-fold in the STRO-1+/Glycophorin A population than in the STRO-1+/Glycophorin A+ population.55 A STRO-1+ enriched subset of marrow cells is capable of differentiating into multiple mesenchymal lineages including hematopoiesis-supportive stromal cells with a vascular smooth muscle-like phenotype, adipocytes, osteoblasts and chondrocytes.56, 57, 58, 59 STRO-1 is a valuable Ab for the identification, isolation and functional characterization of human bone marrow stromal cell precursors, which are quite distinct from those of primitive HSCs.

Neural Stem Cell Markers

Nestin: Nestin is a class VI intermediate filament protein.60,61 Although it is expressed predominantly in stem cells of the central nervous system (CNS),62 its expression is absent from nearly all mature CNS cells.63 Nestin has been the most extensively used marker to identify CNS stem cells within various areas of the developing nervous system and in cultured cells in vitro.34, 64, 65, 66, 67,68 The role of nestin in CNS stem cell biology, however, remains undefined. Although nestin does not form intermediate filaments by itself in vitro it does co-assemble with vimentin or alpha-internexin to form and heterodimer, coiled-coil complexes that may then form intermediate filaments.69 Its transient expression has been suggested to be a major step in the neural differentiation pathway.61 Nestin expression has also been discovered in non-neural stem cell populations, such as pancreatic islet progenitors70, 71, 72 as well as hematopoietic progenitors.73

PSA-NCAM (Polysialic acid-neural cell adhesion molecule): The regulated expression of neural cell adhesion molecule (NCAM) isoforms in the brain is critical for many neural developmental processes. The embryonic form of NCAM, PSA-NCAM, is highly polysialylated and is mainly expressed in the developing nervous system.74 PSA-NCAM may be related to synaptic rearrangement and plasticity.75 In the adult, PSA-NCAM expression is restricted to regions that retain plasticity.76A neuronal-restricted precursor identified by its high expression of PSA-NCAM can undergo self-renewal and differentiate into multiple neuronal phenotypes.77PSA-NCAM+ neonatal brain precursors are restricted to a glial fate and thyroid hormone can modulate them into an oligodendrocyte fate.78, 79, 80 Polysialic acid modification significantly decreases NCAM adhesiveness and therefore, it was originally suggested PSA-NCAM works as a purely anti-adhesive factor that modulates cell-cell interactions in promoting brain plasticity. Increasing evidence indicates that PSA-NCAM may interact with secreted signaling molecules to perform an instructive role in development.81, 82

The structure of NGF with a model of the p75 Neurotrophin Receptor.
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Figure 3. The structure of NGF with a model of the p75 Neurotrophin Receptor. The extracellular domain of the receptor is taken from the tumor necrosis factor receptor structure and the intracellular portion contains a death domain.

p75 Neurotrophin R (NTR): p75 NTR, also named low affinity nerve growth factor (NGF) receptor, is a type I transmembrane protein that belongs to the tumor necrosis factor receptor superfamily (Figure 3).83 It binds to NGF, BDNF, NT-3 and NT-4 equally (with low affinity). p75NTR, when activated in the presence of Trk, enhances responses to neurotrophin (see reference 84 for a review). TrkC receptors working together with p75 NTR have been suggested to serve critical functions during the development of the nervous system.85 Neural crest stem cells (NCSCs) have been isolated based on their surface expression of p75NTR.86,87 Freshly isolated p75NTR+ NCSCs from peripheral nerve tissues can self-renew and generate neurons and glia both in vitro and in vivo. In addition, neuroepithelial-derived p75NTR+ cells are also able to differentiate into neurons, smooth muscle and Schwann cells in culture.88 Recently, p75 NTR has been used as a marker to identify mesenchymal precursors as well as hepatic stellate cells.89, 90


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