Alkaline phosphatase is an enzyme commonly expressed in almost all living organisms. In humans and other mammals, determinations of the expression and activity of alkaline phosphatase have frequently been used for cell determination in developmental studies and/or within clinical trials. Alkaline phosphatase also seems to be one of the key markers in the identification of pluripotent embryonic stem as well as related cells. However, alkaline phosphatases exist in some isoenzymes and isoforms, which have tissue specific expressions and functions. Here, the role of alkaline phosphatase as a stem cell marker is discussed in detail. First, we briefly summarize contemporary knowledge of mammalian alkaline phosphatases in general. Second, we focus on the known facts of its role in and potential significance for the identification of stem cells.

Institute of Biophysics Academy of Sciences of the Czech Republic v v i Královopolská 135 612 65 Brno Czech Republic ; Department of Histology and Embryology Faculty of Medicine Masaryk University Kamenice 5 625 00 Brno Czech Republic

Institute of Experimental Biology Faculty of Science Masaryk University Kotlářská 2 611 37 Brno Czech Republic

Institute of Experimental Biology Faculty of Science Masaryk University Kotlářská 2 611 37 Brno Czech Republic ; International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno Pekařská 53 656 91 Brno Czech Republic

Zobrazit více v PubMed

Kim E. E., Wyckoff H. W. Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. Journal of Molecular Biology. 1991;218(2):449–464. doi: 10.1016/0022-2836(91)90724-k. PubMed DOI

Le Du M. H., Stigbrand T., Taussig M. J., Ménez A., Stura E. A. Crystal structure of alkaline phosphatase from human placenta at 1.8 Å resolution: implication for a substrate specificity. The Journal of Biological Chemistry. 2001;276(12):9158–9165. doi: 10.1074/jbc.m009250200. PubMed DOI

Kozlenkov A., Manes T., Hoylaerts M. F., Millán J. L. Function assignment to conserved residues in mammalian alkaline phosphatases. The Journal of Biological Chemistry. 2002;277(25):22992–22999. doi: 10.1074/jbc.m202298200. PubMed DOI

Le Du M.-H., Millán J. L. Structural evidence of functional divergence in human alkaline phosphatases. The Journal of Biological Chemistry. 2002;277(51):49808–49814. doi: 10.1074/jbc.m207394200. PubMed DOI

Moss D. W. Alkaline phosphatase isoenzymes. Clinical Chemistry. 1982;28(10):2007–2016. PubMed

Hahnel A. C., Rappolee D. A., Millan J. L., et al. Two alkaline phosphatase genes are expressed during early development in the mouse embryo. Development. 1990;110(2):555–564. PubMed

Millán J. L. Mammalian Alkaline Phosphatases. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2006.

McComb R. M., Bowers G. N., Posen S. Alkaline Phosphatase. New York, NY, USA: Springer; 2011.

Kovaříková M., Pacherník J., Hofmanová J., Zadák Z., Kozubík A. TNF-alpha modulates the differentiation induced by butyrate in the HT-29 human colon adenocarcinoma cell line. European Journal of Cancer. 2000;36(14):1844–1852. doi: 10.1016/s0959-8049(00)00178-7. PubMed DOI

Krejčová D., Procházková J., Kubala L., Pacherník J. Modulation of cell proliferation and differentiation of human lung carcinoma cells by the interferon-alpha. General Physiology and Biophysics. 2009;28(3):294–301. doi: 10.4149/gpb_2009_03_294. PubMed DOI

McCormick C., Freshney R. I., Speirs V. Activity of interferon α, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells. British Journal of Cancer. 1995;71(2):232–239. doi: 10.1038/bjc.1995.49. PubMed DOI PMC

Lepire M. L., Ziomek C. A. Preimplantation mouse embryos express a heat-stable alkaline phosphatase. Biology of Reproduction. 1989;41(3):464–473. doi: 10.1095/biolreprod41.3.464. PubMed DOI

Ginsburg M., Snow M. H. L., McLaren A. Primordial germ cells in the mouse embryo during gastrulation. Development. 1990;110(2):521–528. PubMed

Pinkerton J. H., McKay D. G., Adams E. C., Hertig A. T. Development of the human ovary—a study using histochemical technics. Obstetrics and Gynecology. 1961;18:152–181. PubMed

Stoop H., Honecker F., Cools M., de Krijger R., Bokemeyer C., Looijenga L. H. J. Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study. Human Reproduction. 2005;20(6):1466–1476. doi: 10.1093/humrep/deh800. PubMed DOI

Franke F. E., Pauls K., Rey R., Marks A., Bergmann M., Steger K. Differentiation markers of Sertoli cells and germ cells in fetal and early postnatal human testis. Anatomy and Embryology. 2004;209(2):169–177. doi: 10.1007/s00429-004-0434-x. PubMed DOI

Hustin J., Gillerot Y., Franchimont P., Collette J. Placental alkaline phosphatase in developing normal and abnormal gonads and in germ-cell tumours. Virchows Archiv A. 1990;417(1):67–72. doi: 10.1007/bf01600111. PubMed DOI

Hustin J., Collette J., Franchimont P. Immunohistochemical demonstration of placental alkaline phosphatase in various states of testicular development and in germ cell tumours. International Journal of Andrology. 1987;10(1):29–35. doi: 10.1111/j.1365-2605.1987.tb00162.x. PubMed DOI

MacGregor G. R., Zambrowicz B. P., Soriano P. Tissue non-specific alkaline phosphatase is expressed in both embryonic and extraembryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. Development. 1995;121(5):1487–1496. PubMed

Langer D., Ikehara Y., Takebayashi H., Hawkes R., Zimmermann H. The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones. Neuroscience. 2007;150(4):863–879. doi: 10.1016/j.neuroscience.2007.07.064. PubMed DOI

Kermer V., Ritter M., Albuquerque B., Leib C., Stanke M., Zimmermann H. Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation. Neuroscience Letters. 2010;485(3):208–211. doi: 10.1016/j.neulet.2010.09.013. PubMed DOI

Bossi M., Hoylaerts M. F., Millán J. L. Modifications in a flexible surface loop modulate the isozyme-specific properties of mammalian alkaline phosphatases. Journal of Biological Chemistry. 1993;268(34):25409–25416. PubMed

Narisawa S., Hasegawa H., Watanabe K., Millan J. L. Stage-specific expression of alkaline phosphatase during neural development in the mouse. Developmental Dynamics. 1994;201(3):227–235. doi: 10.1002/aja.1002010306. PubMed DOI

Hýžd'alová M., Hofmanová J., Pacherník J., Vaculová A., Kozubík A. The interaction of butyrate with TNF-alpha during differentiation and apoptosis of colon epithelial cells: Role of NF-kappaB activation. Cytokine. 2008;44(1):33–43. doi: 10.1016/j.cyto.2008.06.003. PubMed DOI

Barnard J. A., Warwick G. Butyrate rapidly induces growth inhibition and differentiation in HT-29 cells. Cell Growth & Differentiation. 1993;4(6):495–501. PubMed

Hodin R. A., Meng S., Archer S., Tang R. Cellular growth state differentially regulates enterocyte gene expression in butyrate-treated HT-29 cells. Cell Growth & Differentiation. 1996;7(5):647–653. PubMed

Hull W. E., Halford S. E., Gutfreund H., Sykes B. D. 31P nuclear magnetic resonance study of alkaline phosphatase: the role of inorganic phosphate in limiting the enzyme turnover rate at alkaline pH. Biochemistry. 1976;15(7):1547–1561. doi: 10.1021/bi00652a028. PubMed DOI

Zhang L., Balcerzak M., Radisson J., et al. Phosphodiesterase activity of alkaline phosphatase in ATP-initiated Ca+2 and phosphate deposition in isolated chicken matrix vesicles. The Journal of Biological Chemistry. 2005;280(44):37289–37296. doi: 10.1074/jbc.m504260200. PubMed DOI

Cox R. P., Gilbert P., Jr., Griffin M. J. Alkaline inorganic pyrophosphatase activity of mammalian-cell alkaline phosphatase. Biochemical Journal. 1967;105(1):155–161. PubMed PMC

Georgatsos J. G. Specificity and phosphotransferase activity of purified placental alkaline phosphatase. Archives of Biochemistry and Biophysics. 1967;121(3):619–624. doi: 10.1016/0003-9861(67)90046-x. PubMed DOI

Stinson R. A., McPhee J. L., Collier H. B. Phosphotransferase activity of human alkaline phosphatases and the role of enzyme Zn2+ . Biochimica et Biophysica Acta—Protein Structure and Molecular. 1987;913(3):272–278. doi: 10.1016/0167-4838(87)90135-x. PubMed DOI

Hofmann M. C., Millan J. L. Developmental expression of alkaline phosphatase genes; reexpression in germ cell tumours and in vitro immortalized germ cells. European Urology. 1993;23(1):38–45. PubMed

Ulbright T. M. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Modern Pathology. 2005;18(2):S61–S79. doi: 10.1038/modpathol.3800310. PubMed DOI

Fishman W. H., Inglis N. R., Green S., et al. Immunology and biochemistry of Regan isoenzyme of alkaline phosphatase in human cancer. Nature. 1968;219(5155):697–699. doi: 10.1038/219697a0. PubMed DOI

Li M., Gao J., Feng R., et al. Generation of monoclonal antibody MS17-57 targeting secreted alkaline phosphatase ectopically expressed on the surface of gastrointestinal cancer cells. PLoS ONE. 2013;8(10) doi: 10.1371/journal.pone.0077398.e77398 PubMed DOI PMC

Goldsmith J. D., Pawel B., Goldblum J. R., et al. Detection and diagnostic utilization of placental alkaline phosphatase in muscular tissue and tumors with myogenic differentiation. The American Journal of Surgical Pathology. 2002;26(12):1627–1633. doi: 10.1097/00000478-200212000-00011. PubMed DOI

Alpers D. H., Mahmood A., Engle M., Yamagishi F., DeSchryver-Kecskemeti K. The secretion of intestinal alkaline phosphatase (IAP) from the enterocyte. Journal of Gastroenterology. 1994;29(supplement 7):63–67. PubMed

Mahmood A., Yamagishi F., Eliakim R., DeSchryver-Kecskemeti K., Gramlich T. L., Alpers D. H. A possible role for rat intestinal surfactant-like particles in transepithelial triacylglycerol transport. The Journal of Clinical Investigation. 1994;93(1):70–80. doi: 10.1172/jci116986. PubMed DOI PMC

Shao J.-S., Engle M., Xie Q., et al. Effect of tissue non-specific alkaline phosphatase in maintenance of structure of murine colon and stomach. Microscopy Research and Technique. 2000;51(2):121–128. doi: 10.1002/1097-0029(20001015)51:260;121::aid-jemt362;3.0.co;2-8. PubMed DOI

Narisawa S., Huang L., Iwasaki A., Hasegawa H., Alpers D. H., Millán J. L. Accelerated fat absorption in intestinal alkaline phosphatase knockout mice. Molecular and Cellular Biology. 2003;23(21):7525–7530. doi: 10.1128/mcb.23.21.7525-7530.2003. PubMed DOI PMC

Mizumori M., Ham M., Guth P. H., Engel E., Kaunitz J. D., Akiba Y. Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum. The Journal of Physiology. 2009;587(14):3651–3663. doi: 10.1113/jphysiol.2009.172270. PubMed DOI PMC

Bates J. M., Akerlund J., Mittge E., Guillemin K. Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host and Microbe. 2007;2(6):371–382. doi: 10.1016/j.chom.2007.10.010. PubMed DOI PMC

Goldberg R. F., Austen W. G., Jr., Zhang X., et al. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(9):3551–3556. doi: 10.1073/pnas.0712140105. PubMed DOI PMC

Suzuki A., Guicheux J., Palmer G., et al. Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation. Bone. 2002;30(1):91–98. doi: 10.1016/s8756-3282(01)00660-3. PubMed DOI

Suzuki A., Palmer G., Bonjour J.-P., Caverzasio J. Regulation of alkaline phosphatase activity by p38 MAP kinase in response to activation of Gi protein-coupled receptors by epinephrine in osteoblast-like cells. Endocrinology. 1999;140(7):3177–3182. PubMed

Rey A., Manen D., Rizzoli R., Ferrari S. L., Caverzasio J. Evidences for a role of p38 MAP kinase in the stimulation of alkaline phosphatase and matrix mineralization induced by parathyroid hormone in osteoblastic cells. Bone. 2007;41(1):59–67. doi: 10.1016/j.bone.2007.02.031. PubMed DOI

Caverzasio J., Manen D. Essential role of Wnt3a-mediated activation of mitogen-activated protein kinase p38 for the stimulation of alkaline phosphatase activity and matrix mineralization in C3H10T1/2 mesenchymal cells. Endocrinology. 2007;148(11):5323–5330. doi: 10.1210/en.2007-0520. PubMed DOI

Allen M., Svensson L., Roach M., Hambor J., McNeish J., Gabel C. A. Deficiency of the stress kinase p38α results in embryonic lethality: characterization of the kinase dependence of stress responses of enzyme-deficient embryonic stem cells. The Journal of Experimental Medicine. 2000;191(5):859–870. doi: 10.1084/jem.191.5.859. PubMed DOI PMC

Kim J. M., White J. M., Shaw A. S., Sleckman B. P. MAPK p38α is dispensable for lymphocyte development and proliferation. Journal of Immunology. 2005;174(3):1239–1244. doi: 10.4049/jimmunol.174.3.1239. PubMed DOI

Tesar P. J., Chenoweth J. G., Brook F. A., et al. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature. 2007;448(7150):196–199. doi: 10.1038/nature05972. PubMed DOI

Brons I. G. M., Smithers L. E., Trotter M. W. B., et al. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. 2007;448(7150):191–195. doi: 10.1038/nature05950. PubMed DOI

Narisawa S., Fröhlander N., Millán J. L. Inactivation of two mouse alkaline phosphatase genes and establishment of a model of infantile hypophosphatasia. Developmental Dynamics. 1997;208(3):432–446. doi: 10.1002/(sici)1097-0177(199703)208:3x003C;432::aid-aja13x0003e;3.0.co;2-1. PubMed DOI

Buehr M. The primordial germ cells of mammals: some current perspectives. Experimental Cell Research. 1997;232(2):194–207. doi: 10.1006/excr.1997.3508. PubMed DOI

Shimada N., Yamada K., Tanaka T., et al. Alterations of gene expression in endoderm differentiation of F9 teratocarcinoma cells. Molecular Reproduction and Development. 2001;60(2):165–171. doi: 10.1002/mrd.1073. PubMed DOI

Zwaka T. P., Thomson J. A. A germ cell origin of embryonic stem cell? Development. 2005;132(2):227–233. doi: 10.1242/dev.01586. PubMed DOI

Mulivor R. A., Plotkin L. I., Harris H. Differential inhibition of the products of the human alkaline phosphatase loci. Annals of Human Genetics. 1978;42(1):1–13. doi: 10.1111/j.1469-1809.1978.tb00927.x. PubMed DOI

van Belle H. Alkaline phosphatase. I. Kinetics and inhibition by levamisole of purified isoenzymes from humans. Clinical Chemistry. 1976;22(7):972–976. PubMed

Komoda T., Hokari S., Sonoda M., Sakagishi Y., Tamura T. L-phenylalanine inhibition of human alkaline phosphatases with p-nitrophenyl phosphate as substrate. Clinical Chemistry. 1982;28(12):2426–2428. PubMed

Lin C. W., Sie H. G., Fishman W. H. L-tryptophan. A non-allosteric organ-specific uncompetitive inhibitor of human placental alkaline phosphatase. Biochemical Journal. 1971;124(3):509–516. PubMed PMC

Doellgast G. J., Fishman W. H. L leucine a specific inhibitor of a rare human placental alkaline phosphatase phenotype. Nature. 1976;259(5538):49–51. doi: 10.1038/259049a0. PubMed DOI

Fishman W. H., Sie H.-G. L-Homoarginine; an inhibitor of serum “bone and liver” alkaline phosphatase. Clinica Chimica Acta. 1970;29(2):339–341. doi: 10.1016/0009-8981(70)90057-4. PubMed DOI

Brunel C., Cathala G. Imidazole: aan inhibitor of l-phenylalanine-insensitive alkaline phosphatases of tissues other than intestine and placenta. Biochimica et Biophysica Acta—Enzymology. 1972;268(2):415–421. PubMed

Nouwen E. J., Hendrix P. G., Dauwe S., Eerdekens M. W., de Broe M. E. Tumor markers in the human ovary and its neoplasms. A comparative immunohistochemical study. The American Journal of Pathology. 1987;126(2):230–242. PubMed PMC

O'Connor M. D., Kardel M. D., Iosfina I., et al. Alkaline phosphatase-positive colony formation is a sensitive, specific, and quantitative indicator of undifferentiated human embryonic stem cells. Stem Cells. 2008;26(5):1109–1116. doi: 10.1634/stemcells.2007-0801. PubMed DOI

Pera M. F., Reubinoff B., Trounson A. Human embryonic stem cells. Journal of Cell Science. 2000;113(1):5–10. PubMed

Ginis I., Luo Y., Miura T., et al. Differences between human and mouse embryonic stem cells. Developmental Biology. 2004;269(2):360–380. doi: 10.1016/j.ydbio.2003.12.034. PubMed DOI

Andäng M., Hjerling-Leffler J., Moliner A., et al. Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation. Nature. 2008;451(7177):460–464. doi: 10.1038/nature06488. PubMed DOI

Yamanaka S., Takahashi K. Induction of pluripotent stem cells from mouse fibroblast cultures. Tanpakushitsu Kakusan Koso: Protein, Nucleic Acid, Enzyme. 2006;51(15):2346–2351. PubMed

Loh Y.-H., Wu Q., Chew J.-L., et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genetics. 2006;38(4):431–440. doi: 10.1038/ng1760. PubMed DOI

González F., Boué S., Belmonte J. C. I. Methods for making induced pluripotent stem cells: reprogramming à la carte. Nature Reviews Genetics. 2011;12(4):231–242. doi: 10.1038/nrg2937. PubMed DOI

Williams R. L., Hilton D. J., Pease S., et al. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 1988;336(6200):684–687. doi: 10.1038/336684a0. PubMed DOI

Rohwedel J., Guan K., Wobus A. M. Induction of cellular differentiation by retinoic acid in vitro. Cells Tissues Organs. 1999;165(3-4):190–202. doi: 10.1159/000016699. PubMed DOI

Mark M., Ghyselinck N. B., Chambon P. Function of retinoic acid receptors during embryonic development. Nuclear Receptor Signaling. 2009;7, article e002 PubMed PMC

Mummery C. L., Feyen A., Freund E., Shen S. Characteristics of embryonic stem cell differentiation: a comparison with two embryonal carcinoma cell lines. Cell Differentiation and Development. 1990;30(3):195–206. doi: 10.1016/0922-3371(90)90139-n. PubMed DOI

Pacherník J., Ešner M., Bryja V., Dvořák P., Hampl A. Neural differentiation of mouse embryonic stem cells grown in monolayer. Reproduction Nutrition Development. 2002;42(4):317–326. doi: 10.1051/rnd:2002028. PubMed DOI

Pacherník J., Bryja V., Ešner M., Kubala L., Dvořák P., Hampl A. Neural differentiation of pluripotent mouse embryonal carcinoma cells by retinoic acid: inhibitory effect of serum. Physiological Research. 2005;54(1):115–122. PubMed

Kotasová H., Veselá I., Kučera J., et al. Phosphoinositide 3-kinase inhibition enables retinoic acid-induced neurogenesis in monolayer culture of embryonic stem cells. Journal of Cellular Biochemistry. 2012;113(2):563–570. doi: 10.1002/jcb.23380. PubMed DOI

Gianni' M., Studer M., Carpani G., Terao M., Garattini E. Retinoic acid induces liver/bone/kidney-type alkaline phosphatase gene expression in F9 teratocarcinoma cells. The Biochemical Journal. 1991;274(3):673–678. PubMed PMC

Scheibe R. J., Moeller-Runge I., Mueller W. H. Retinoic acid induces the expression of alkaline phosphatase in P19 teratocarcinoma cells. The Journal of Biological Chemistry. 1991;266(31):21300–21305. PubMed

Preclíková H., Bryja V., Pacherník J., Krejčí P., Dvořák P., Hampl A. Early cycling-independent changes to p27, cyclin D2, and cyclin D3 in differentiating mouse embryonal carcinoma cells. Cell Growth and Differentiation. 2002;13(9):421–430. PubMed

Bryja V., Pacherník J., Vondráček J., et al. Lineage specific composition of cyclin D-CDK4/CDK6-p27 complexes reveals distinct functions of CDK4, CDK6 and individual D-type cyclins in differentiating cells of embryonic origin. Cell Proliferation. 2008;41(6):875–893. doi: 10.1111/j.1365-2184.2008.00556.x. PubMed DOI PMC

Bryja V., Pacherník J., Souček K., Horvath V., Dvořák P., Hampl A. Increased apoptosis in differentiating p27-deficient mouse embryonic stem cells. Cellular and Molecular Life Sciences. 2004;61(11):1384–1400. doi: 10.1007/s00018-004-4081-4. PubMed DOI PMC

Nayernia K., Nolte J., Michelmann H. W., et al. In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice. Developmental Cell. 2006;11(1):125–132. doi: 10.1016/j.devcel.2006.05.010. PubMed DOI

Elliott A. M., de Miguel M. P., Rebel V. I., Donovan P. J. Identifying genes differentially expressed between PGCs and ES cells reveals a role for CREB-binding protein in germ cell survival. Developmental Biology. 2007;311(2):347–358. doi: 10.1016/j.ydbio.2007.08.029. PubMed DOI

Pikarsky E., Sharir H., Ben-Shushan E., Bergman Y. Retinoic acid represses Oct-3/4 gene expression through several retinoic acid-responsive elements located in the promoter-enhancer region. Molecular and Cellular Biology. 1994;14(2):1026–1038. PubMed PMC

Kim J. S., Kim B. S., Kim J., Park C.-S., Chung I. Y. The phosphoinositide-3-kinase/Akt pathway mediates the transient increase in Nanog expression during differentiation of F9 cells. Archives of Pharmacal Research. 2010;33(7):1117–1125. doi: 10.1007/s12272-010-0719-y. PubMed DOI

Hallmann D., Trümper K., Trusheim H., et al. Altered signaling and cell cycle regulation in embryonal stem cells with a disruption of the gene for phosphoinositide 3-kinase regulatory subunit p85α . The Journal of Biological Chemistry. 2003;278(7):5099–5108. doi: 10.1074/jbc.m208451200. PubMed DOI PMC

Paling N. R. D., Wheadon H., Bone H. K., Welham M. J. Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling. The Journal of Biological Chemistry. 2004;279(46):48063–48070. PubMed

Rodda D. J., Chew J.-L., Lim L.-H., et al. Transcriptional regulation of Nanog by OCT4 and SOX2. Journal of Biological Chemistry. 2005;280(26):24731–24737. doi: 10.1074/jbc.M502573200. PubMed DOI

Pan G., Li J., Zhou Y., Zheng H., Pei D. A negative feedback loop of transcription factors that controls stem cell pluripotency and self-renewal. The FASEB Journal. 2006;20(10):1730–1732. doi: 10.1096/fj.05-5543fje. PubMed DOI

Yamaguchi S., Kurimoto K., Yabuta Y., et al. Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. Development. 2009;136(23):4011–4020. doi: 10.1242/dev.041160. PubMed DOI

Heine P., Braun N., Heilbronn A., Zimmermann H. Functional characterization of rat ecto-ATPase and ecto-ATP diphosphohydrolase after heterologous expression in CHO cells. European Journal of Biochemistry. 1999;262(1):102–107. doi: 10.1046/j.1432-1327.1999.00347.x. PubMed DOI

Jaiswal R. K., Jaiswal N., Bruder S. P., Mbalaviele G., Marshak D. R., Pittenger M. F. Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. The Journal of Biological Chemistry. 2000;275(13):9645–9652. doi: 10.1074/jbc.275.13.9645. PubMed DOI

Bühring H.-J., Treml S., Cerabona F., De Zwart P., Kanz L., Sobiesiak M. Phenotypic characterization of distinct human bone marrow-derived MSC subsets. Annals of the New York Academy of Sciences. 2009;1176:124–134. doi: 10.1111/j.1749-6632.2009.04564.x. PubMed DOI

Gargett C. E., Masuda H. Adult stem cells in the endometrium. Molecular Human Reproduction. 2010;16(11):818–834. doi: 10.1093/molehr/gaq061. PubMed DOI

Sobiesiak M., Sivasubramaniyan K., Hermann C., et al. The mesenchymal stem cell antigen MSCA-1 is identical to tissue non-specific alkaline phosphatase. Stem Cells and Development. 2010;19(5):669–677. doi: 10.1089/scd.2009.0290. PubMed DOI

Kim Y. H., Yoon D. S., Kim H. O., Lee J. W. Characterization of different subpopulations from bone marrow-derived mesenchymal stromal cells by alkaline phosphatase expression. Stem Cells and Development. 2012;21(16):2958–2968. doi: 10.1089/scd.2011.0349. PubMed DOI PMC

Kenmotsu M., Matsuzaka K., Kokubu E., Azuma T., Inoue T. Analysis of side population cells derived from dental pulp tissue. International Endodontic Journal. 2010;43(12):1132–1142. doi: 10.1111/j.1365-2591.2010.01789.x. PubMed DOI PMC

Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs

Clinical-Grade Human Pluripotent Stem Cells for Cell Therapy: Characterization Strategy

Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells