Skip to main content
Log in

Pluripotent stem cells: Maintenance of genetic and epigenetic stability and prospects of cell technologies

  • Reviews
  • Published:
Russian Journal of Developmental Biology Aims and scope Submit manuscript

Abstract

Permanent lines of pluripotent stem cells can be obtained from humans and monkeys using different techniques and from different sources—inner cell mass of the blastocyst, primary germ cells, parthenogenetic oocytes, and mature spermatogonia—as well as by transgenic modification of various adult somatic cells. Despite different origin, all pluripotent lines demonstrate considerable similarity of the major biological properties: active self-renewal and differentiation into various somatic and germ cells in vitro and in vivo, similar gene expression profiles, and similar cell cycle structure. Ten years of intense studies on the stability of different human and monkey embryonic stem cells demonstrated that, irrespective of their origin, long-term in vitro cultures lead to the accumulation of chromosomal and gene mutations as well as epigenetic changes that can cause oncogenic transformation of cells. This review summarizes the research data on the genetic and epigenetic stability of different lines of pluripotent stem cells after long-term in vitro culture. These data were used to analyze possible factors of the genome and epigenome instability in pluripotent lines. The prospects of using pluripotent stem cells of different origin in cell therapy and pharmacological studies were considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adewumi, O., Aflatoonian, B., Ahrlund-Richter, L., et al., Characterization of Human Embryonic Stem Cell Lines by the International Stem Cell Initiative, Nat. Biotech., 2007, vol. 25, pp. 803–816.

    Article  CAS  Google Scholar 

  • Allegrucci, C. and Young, L.E., Differences between Human Embryonic Stem Cell Lines, Hum. Repr. Update, 2007, vol. 13, no. 2, pp. 103–120.

    Article  CAS  Google Scholar 

  • Andrews, P.W., From Teratocarcinomas to Embryonic Stem Cells, Philos. Trans. R. Soc. Lond. B. Biol Sci., 2002, vol. 357, pp. 405–417.

    Article  PubMed  Google Scholar 

  • Beattie, G.M., Lopez, A.D., Bucay, N., et al., Activin A Maintains Pluripotency of Human Embryonic Stem Cells in the Absence of Feeder Layers, Stem Cells, 2005, vol. 23, pp. 489–495.

    Article  PubMed  CAS  Google Scholar 

  • Becker, K.A., Ghule, P.N., Therrien, J.A., et al., Self-Renewal of Human Embryonic Stem Cells Is Supported by a Shortened G1 Cell Cycle Phase, J. Cell Physiol., 2006, vol. 209, pp. 883–893.

    Article  PubMed  CAS  Google Scholar 

  • Becker, K.A., Stein, J.L., Lian, J.B., et al., Establishment of Histone Gene Regulation and Cell Cycle Checkpoint Control in Human Embryonic Stem Cells, J. High Resolut. Chromatogr. Chromatogr. Commun., 2007, vol. 210, pp. 517–526.

    CAS  Google Scholar 

  • Bhattacharia, B., Miura, T., Brandenberger, R., et al., Gene Expression in Human Embryonic Stem Cell Lines: Unique Molecular Signature, Blood, 2004, vol. 103, no. 8, pp. 2956–2961.

    Article  CAS  Google Scholar 

  • Bigdeli, N., Andersson, M., Strehl, R., et al., Adaptation of Human Embryonic Stem Cells to Feeder-Free and Matrix-Free Culture Conditions Directly on Plastic Surfaces, J. Biotechnol., 2008, vol. 133, no. 1, pp. 146–153.

    Article  PubMed  CAS  Google Scholar 

  • Brandenberger, R., Khrebtukova, I., Thies, R.S., et al., MPSS Profiling of Human Embryonic Stem Cells, BMC Devel. Biol., 2004, vol. 4, pp. 1–16.

    Article  Google Scholar 

  • Brimble, S.N., Zeng, X., Weiler, D.A., et al., Karyotypic Stability, Genotyping, Differentiation, Feeder-Free Maintenance, and Gene Expression Sampling in Three Human Embryonic Stem Cell Lines Derived prior to August 9, 2001, Stem Cells Devel., 2004, vol. 13, pp. 585–597.

    Article  CAS  Google Scholar 

  • Burbee, D.G., Forgacs, E., Zochbauer-Muller, S., et al., Epigenetic Inactivation of RASSF1A in Lung and Breast Cancers and Malignant Phenotype Suppression, J. Natl. Cancer Inst., 2001, vol. 93, pp. 691–699.

    Article  PubMed  CAS  Google Scholar 

  • Burdon, T., Smith, A., and Savatier, P., Signaling, Cell Cycle and Pluripotency in Embryonic Stem Cells, Trends Cell Biol., 2002, vol. 12, pp. 432–438.

    Article  PubMed  CAS  Google Scholar 

  • Buzzard, J.J., Gough, N.M., Crook, J.M., and Colman, A., Karyotype of Human ES Cells during Extended Culture, Nat. Biotechnol., 2004, vol. 22, pp. 381–382.

    Article  PubMed  CAS  Google Scholar 

  • Byrne, J.A., Pedersen, D.A., Clepper, L.L., et al., Producing Primate Embryonic Stem Cells by Somatic Cell Nuclear Transfer, Nature, 2007, vol. 450, pp. 497–505.

    Article  PubMed  CAS  Google Scholar 

  • Caisander, G., Park, H., Frej, K., et al., Chromosomal Integrity Maintained in Five Human Embryonic Stem Cell Lines after Prolonged in Vitro Culture, Chromosome Res., 2006, vol. 14, pp. 131–137.

    Article  PubMed  CAS  Google Scholar 

  • Cibelli, J.B., Grant, K.A., Chapman, K.B., et al., Parthenogenetic Stem Cells in Nonhuman Primates, Science, 2002, vol. 295, p. 819.

    Article  PubMed  CAS  Google Scholar 

  • Clark, A.T., Rodrigues, R.T., Bodnar, M.S., et al., Human STELLAR, NANOG, and GDF3 Genes Are Expressed in Pluripotent Cells and Map to Chromosome 12p13, A Hotspot for Teratocarcinoma, Stem Cells, 2004, vol. 22, pp. 169–179.

    Article  PubMed  CAS  Google Scholar 

  • Cowan, C.A., Atienza, J., Melton, D.A., and Eggan, K., Nuclear Reprogramming of Somatic Cells after Fusion with Human Embryonic Stem Cells, Science, 2005, vol. 309, pp. 1369–1373.

    Article  PubMed  CAS  Google Scholar 

  • Cowan, C.A., Klimanskaya, I., McMahon, J., et al., Derivation of Embryonic Stem-Cell Lines from Human Blastocysts, N. Engl. J. Med., 2004, vol. 50, pp. 1353–1356.

    Article  Google Scholar 

  • Cui, H., Onyango, P., Brandenburg, S., et al., Loss of Imprinting in Colorectal Cancer Linked to Hypomethylation of H19 and IGF2, Cancer Res., 2002, vol. 62, pp. 6442–6446.

    PubMed  CAS  Google Scholar 

  • Dighe, V., Clepper, L., Pedersen, D., et al., Heterozygous Embryonic Stem Cell Lines Derived from Nonhuman Primate Parthenotes, Stem Cells, 2008, pp. 756–766.

  • Draper, J.S., Smith, K., Gokhale, P., et al., Recurrent Gain of Chromosomes 17q and 12 in Cultured Human Embryonic Stem Cells, Nat. Biotechnol., 2004, vol. 22, pp. 53–54.

    Article  PubMed  CAS  Google Scholar 

  • Enver, T., Soneji, S., Joshi, C., et al., Cellular Differentiation Hierarchies in Normal and Culture-Adapted Human Embryonic Stem Cells, Hum. Mol. Genet., 2005, vol. 14, pp. 3129–3140.

    Article  PubMed  CAS  Google Scholar 

  • Fang, D., Leishear, K., Nguyen, T.K., et al., Defining the Conditions for the Generation of Melocytes from Human Embryonic Stem Cells, Stem Cells, 2006, vol. 24, pp. 1668–1677.

    Article  PubMed  Google Scholar 

  • Feinberg, A.P. and Tycko, B., The History of Cancer Epigenetics, Nat. Rev. Cancer, 2004, vol. 4, pp. 143–153.

    Article  PubMed  CAS  Google Scholar 

  • Fluckiger, A.C., Marcy, G., Marchand, M., et al., Cell Cycle Features of Primate Embryonic Stem Cells, Stem Cells, 2006, vol. 24, pp. 547–556.

    Article  PubMed  CAS  Google Scholar 

  • French, A.J., Adams, C.A., Anderson, L.S., et al., Development of Human Cloned Blastocysts Following Somatic Nuclear Transfer (SCNT) with Adult Fibroblast, J. High Resolut. Chromatogr. Chromatogr. Commun., 2008, vol. 26, pp. 485–493.

    CAS  Google Scholar 

  • Fujimoto, A., Mitalipov, S.M., Clepper, L.L., and Wolf, D.P., Development of a Monkey Model for the Study of Primate Genomic Imprinting, Mol. Hum. Reprod., 2005, vol. 11, pp. 413–422.

    Article  PubMed  CAS  Google Scholar 

  • Gerami-Naini, B., Dovzhenk, O.V., Durning, M., et al., Trophoblast Differentiation in Embryoid Bodies Derived from Human Embryonic Stem Cells, Endocrinology, 2004, vol. 145, pp. 1517–1524.

    Article  PubMed  CAS  Google Scholar 

  • Gordeeva, O.F., Pluripotent Cells in Embryogenesis and in Teratoma Formation, in Stem Cells and Cancer, Parsons, D.W., Wd., New York: Nova Sci., 2007, pp. 62–85.

    Google Scholar 

  • Gordeeva, O.F., Krasnikova, N.Yu., Larionova, A.V., et al., Analysis of Expression of Genes Specific for Pluripotent and Primordial Germ Cells in Human and Mouse Embryonic Stem Cell Lines, Dokl. Akad. Nauk, 2006, vol. 406, no. 6, pp. 835–839.

    Google Scholar 

  • Hanson, C. and Caisander, G., Human Embryonic Stem Cells and Chromosome Stability, Apmis, 2005, vol. 113, pp. 751–755.

    Article  PubMed  Google Scholar 

  • Heins, N., Englund, M.C., Sjoblom, C., et al., Derivation, Characterization, and Differentiation of Human Embryonic Stem Cells, Stem Cells, 2004, vol. 22, pp. 367–376.

    Article  PubMed  Google Scholar 

  • Hernandez, L., Kozlov, S., Piras, G., and Stewart, C.L., Paternal and Maternal Genomes Confer Opposite Effects on Proliferation, Cell-Cycle Length, Senescence, and Tumor Formation, Proc. Natl. Acad. Sci. USA, 2003, vol. 100, pp. 13344–13349.

    Article  PubMed  CAS  Google Scholar 

  • Herszfeld, D., Wolvetang, E., Langton-Bunker, E., et al., CD30 Is a Survival Factor and a Biomarker for Tranformed Human Pluripotent Stem Cells, Nat. Biotechnol., 2006, vol. 24, pp. 351–357.

    Article  PubMed  CAS  Google Scholar 

  • Hoffman, L.M., Hall, L., Batten, J.L., et al., X-Inactivation Status Varies in Human Embryonic Stem Cell Lines, Stem Cells, 2005, vol. 23, pp. 1468–1478.

    Article  PubMed  CAS  Google Scholar 

  • Hovatta, O., Mikkola, M., Gertow, K., et al., A Culture System Using Human Foreskin Fibroblasts as Feeder Cells Allows Production of Human Embryonic Stem Cells, Hum. Reprod., 2003, vol. 18, pp. 1404–1409.

    Article  PubMed  Google Scholar 

  • Hsiao, L.L., Dangond, F., Yoshida, T., et al., A Compendium of Gene Expression in Normal Human Tissues, Physiol Genomics, 2001, vol. 7, pp. 97–104.

    PubMed  CAS  Google Scholar 

  • Inzunza, J., Sahlen, S., Holmberg, K., et al., Comparative Genomic Hybridization and Karyotyping of Human Embryonic Stem Cells Reveals the Occurence of An Isodicentric X Chromosome after Long-Term Cultivation, Mol. Hum. Reprod., 2004, vol. 10, pp. 461–466.

    Article  PubMed  CAS  Google Scholar 

  • Jaenisch, R. and Bird, A., Epigenetic Regulation of Gene Expression: How the Genome Integrates Intrinsic and Environmental Signals, Nat. Genet., 2003, vol. 33, pp. 245–254.

    Article  PubMed  CAS  Google Scholar 

  • Kim, S.J., Lee, J.E., Park, J.H., et al., Efficient Derivation of New Human Embryonic Stem Cell Lines, Mol. Cells, 2005, vol. 19, pp. 46–53.

    PubMed  CAS  Google Scholar 

  • Klimanskaya, I., Chung, Y., Becker, S., et al., Human Embryonic Stem Cell Lines Derived from Single Blastomeres, Nature, 2006, vol. 444, no. 7118, pp. 481–485.

    Article  PubMed  CAS  Google Scholar 

  • Lakshmipathy, U., Pelacho, B., Sudo, K., et al., Efficient Transfection of Embryonic and Adult Stem Cells, Stem Cells, 2004, vol. 22, pp. 531–543.

    Article  PubMed  Google Scholar 

  • Lin, G., OuYang, Q., Zhou, X., et al., A Highly Homozygous and Parthenogenetic Human Embryonic Stem Cell Line Derived from a One-Pronuclear Oocyte Following in Vitro Fertilization Procedure, Cell Res, 2007, vol. 17, no. 12, pp. 999–1007.

    Article  PubMed  CAS  Google Scholar 

  • Lin, T., Chao, C., Saito, S., et al., P53 Induces Differentiation of Mouse Embryonic Stem Cells by Suppressing Nanog Expression, Nat. Cell Biol., 2005, vol. 7, pp. 165–171.

    Article  PubMed  CAS  Google Scholar 

  • Maherali, N., Sridharan, R., Xie, W., et al., Directly Reprogrammed Fibroblasts Show Global Epigenetic Remodelling and Widespread Tissue Contribution, Cell Stem Cell, 2007, vol. 1, pp. 55–70.

    Article  PubMed  CAS  Google Scholar 

  • Maitra, A., Arking, D.E., Shivapurkar, N., et al., Genomic Alterations in Cultured Human Embryonic Stem Cells, Nat. Genet., 2005, vol. 37, pp. 1099–1103.

    Article  PubMed  CAS  Google Scholar 

  • Mitalipov, S., Clepper, L., Sritanaudomchai, H., et al., Methylation Status of Imprinting Centers for H19/IGF2 and SNURF/SNRPN in Primate Embryonic Stem Cells, J. High Resolut. Chromatogr. Chromatogr. Commun., 2007, vol. 25, pp. 581–588.

    CAS  Google Scholar 

  • Mitalipov, S., Kuo, H.C., Byrne, J., et al., Isolation and Characterization of Novel Rhesus Monkey Embryonic Stem Cell Lines, Stem Cells, 2006, vol. 24, pp. 2177–2186.

    Article  PubMed  CAS  Google Scholar 

  • Mitalipova, M.M., Rao, R.R., Hoyer, D.M., et al., Preserving the Genetic Integrity of Human Embryonic Stem Cells, Nat. Biotechnol., 005, vol. 23, pp. 19–20.

  • Miura, T., Luo, Y., Khrebtukova, I., et al., Monitoring Early Differentiation Events in Human Embryonic Stem Cells by Massively Parallel Signature Sequencing and Expressed Sequence Tag Scan, Stem Cells Devel., 2004, vol. 13, pp. 694–715.

    Article  CAS  Google Scholar 

  • Miura, M., Miura, Y., Padilla-Nash, H.M., et al., Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation, Stem Cells, 2005, vol. 24, pp. 1095–1103.

    Article  PubMed  Google Scholar 

  • Nakagawa, H., Chadwick, R.B., Peltomaki, P., et al., Loss of Imprinting of the Insulin-Like Growth Factor II Gene Occurs by Biallelic Methylation in a Core Region of H19-Associated CTCF-Binding Sites in Colorectal Cancer, Proc. Natl. Acad. Sci. USA, 2001, vol. 98, pp. 591–596.

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa, M., Koyanagi, M., Tanabe, K., et al., Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts, Nat. Biotech., 2008, vol. 26, pp. 101–106.

    Article  CAS  Google Scholar 

  • Nakatsuji, N. and Suemori, H., Embryonic Stem Cell Lines of Nonhuman Primates, Sci. W. J., 2002, vol. 2, pp. 1762–1773.

    Google Scholar 

  • Nicholls, R.D. and Knepper, J.L., Genome Organization, Function, and Imprinting in Prader-Willi and Angelman Syndromes, Annu. Rev. Genomics Hum. Genet., 2001, vol. 2, pp. 153–175.

    Article  PubMed  CAS  Google Scholar 

  • Nonomura, N., Miki, T., Nishimura, K., et al., Altered Imprinting of the H19 and Insulin-Like Growth Factor II Genes in Testicular Tumors, J. Urol., 1997, vol. 157, pp. 1977–1979.

    Article  PubMed  CAS  Google Scholar 

  • Ohm, J.E., McGarvey, K.M., Yu, X., et al., A Stem Cell-Like Chromatin Pattern May Predispose Tumor Suppressor Genes to DNA Hypermethylation and Heritable Silencing, Nat. Genet., 2007, vol. 39, pp. 237–242.

    Article  PubMed  CAS  Google Scholar 

  • Okano, M., Bell, D.W., Haber, D.A., and Li, E., DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for de Novo Methylation and Mammalian Development, Cell, 1999, vol. 99, no. 3, pp. 247–257.

    Article  PubMed  CAS  Google Scholar 

  • Okita, K., Ichisaka, T., and Yamanaka, S., Generation of Germ-Line Competent Induced Pluripotent Stem Cells, Nature, 2007, vol. 448, pp. 313–317.

    Article  PubMed  CAS  Google Scholar 

  • Onyango, P., Jiang, S., Uejima, H., et al., Monoallelic Expression and Methylation of Imprinted Genes in Human and Mouse Embryonic Germ Cell Lineages, Proc. Natl. Acad. Sci. USA, 2002, vol. 99, pp. 10599–10604.

    Article  PubMed  CAS  Google Scholar 

  • Plaia, T.W., Josephson, R., Liu, Y., et al., Characterization of a New NIH Registeres Variant Human Embryonic Stem Cell Line BG01V: A Tool for Human Embryonic Stem Cell Research, Stem Cells, 2005, vol. 24, pp. 531–546.

    Article  PubMed  CAS  Google Scholar 

  • Przyborski, S.A., Differentiation of Human Embryonic Stem Cells after Transplantation in Immune-Deficient Mice, J. High Resolut. Chromatogr. Chromatogr. Commun., 2005, vol. 2, pp. 1242–1250.

    Google Scholar 

  • Rajesh, D., Chinnasamy, N.M., Mitalipov, S.M., et al., Differential Requirements for Hematopoietic Commitment between Human and Rhesus Embryonic Sem Cells, J. High Resolut. Chromatogr. Chromatogr. Commun., 2007, vol. 25, pp. 490–499.

    CAS  Google Scholar 

  • Rao, R.R., Calhoun, J.D., Qin, X., et al., Comparative Transcriptional Profiling of Two Human Embryonic Stem Cell Lines, Biotech. Bioengin., 2004, vol. 88, no. 3, pp. 273–286.

    Article  CAS  Google Scholar 

  • Revazova, E.S., Turovets, N.A., Kochetkova, O.D., et al., Patient-Specific Stem Cell Lines Derived from Human Parthenogenetic Blastocysts, Cloning Stem Cells, 2007, vol. 9, no. 3, pp. 432–449.

    Article  PubMed  CAS  Google Scholar 

  • Rosler, E.S., Fisk, G.J., Ares, X., et al., Long-Term Culture of Human Embryonic Stem Cells in Feeder-Free Conditions, Devel. Dyn., 2004, vol. 229, pp. 259–274.

    Article  CAS  Google Scholar 

  • Rugg-Gunn, P.J., Ferguson-Smith, A.C., and Pedersen, R.A., Epigenetic Status of Human Embryonic Stem Cells, Nat. Genet., 2005, vol. 37, pp. 585–587.

    Article  PubMed  CAS  Google Scholar 

  • Saretzki, G., Armstrong, L., Leake, A., et al., Stress Defense in Murine Embryonic Stem Cells Is Superior to That of Various Differentiated Murine Cells, Stem Cells, 2004, vol. 22, pp. 962–971.

    Article  PubMed  CAS  Google Scholar 

  • Saretzki, G., Walter, T., Atkinson, S., et al., Downregulation of Multiple Stress Defense Mechanisms during Differentiation of Human Embryonic Stem Cells, Stem Cells, 2008, vol. 26, pp. 455–464.

    Article  PubMed  CAS  Google Scholar 

  • Savatier, P., Huang, S., Szekely, L., et al., Contrasting Patterns of Retinoblastoma Protein Expression in Mouse Embryonic Stem Cells and Embryonic Fibroblasts, Oncogene, 1994, vol. 9, pp. 809–818.

    PubMed  CAS  Google Scholar 

  • Savatier, P. and Lapillonne, H., Grunsven Van, London: A. et al. Withdrawal of Differentiation Inhibitory Activity/Leukemia Inhibitory Factor Up-regulates D Type Cyclins and Cyclin-Dependent Kinase Inhibitors in Mouse Embryonic Stem Cells, Oncogene, 1996, vol. 12, pp. 309–322.

    PubMed  CAS  Google Scholar 

  • Schwanke, K., Wunderlich, S., Reppel, M., et al., Generation and Characterization of Functional Cardiomyocytes from Rhesus Monkey Embryonic Stem Cells, Stem Cells, 2006, vol. 24, pp. 1423–1432.

    Article  PubMed  CAS  Google Scholar 

  • Secombe, J., Pierce, S.B., and Eisenman, R.N., Myc: A Weapon of Mass Destruction, Cell, 2004, vol. 117, pp. 3–156.

    Article  Google Scholar 

  • Shamblott, M.J., Axelman, J., Wang, S., et al., Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells, Proc. Natl. Acad. Sci. USA, 1998, vol. 95, pp. 13726–13731.

    Article  PubMed  CAS  Google Scholar 

  • Shin, S., Mitalipova, M., Noggle, S., et al., Long-Term Proliferation of Human Embryonic Stem Cell-Derived Neuroepithelial Cells Using Defined Adherent Culture Conditions, Stem Cells, 2006, vol. 24, pp. 125–138.

    Article  PubMed  Google Scholar 

  • Skotheim, R.I., Monni, O., Mousses, S., et al., New Insights into Testicular Germ Cell Tumorigenesis from Gene Expression Profiling, Cancer Res., 2002, vol. 62, pp. 2359–2364.

    PubMed  CAS  Google Scholar 

  • Skottman, H., Mikkola, M., Lundin, K., et al., Gene Expression Signatures of Seven Individual Human Embryonic Stem Cell Lines, Stem Cells, 2005, vol. 23, pp. 1343–1356.

    Article  PubMed  CAS  Google Scholar 

  • Soejima, H. and Wagstaff, J., Imprinting Centers, Chromatin Structure, and Disease, J. Cell Biochem, 2005, vol. 95, pp. 226–233.

    Article  PubMed  CAS  Google Scholar 

  • Sperger, J.M., Chen, X., Draper, J.S., et al., Gene Expression Patterns in Human Embryonic Stem Cells and Human Pluripotent Germ Cell Tumors, Proc. Natl. Acad. Sci. USA, 2003, vol. 100, pp. 13350–13355.

    Article  PubMed  CAS  Google Scholar 

  • Strelchenko, N., Verlinsky, O., Kukharenko, V., and Verlinsky, Y., Morula-Derived Human Embryonic Stem Cells, Reprod. Biomed. Online, 2004, vol. 9, no. 6, pp. 623–629.

    Article  PubMed  Google Scholar 

  • Suemori, H., Tada, T., Torii, R., et al., Establishment of Embryonic Stem Cell Lines from Cynomolgus Monkey Blastocysts Produced by IVF Or ICSI, Devel. Dyn., 2001, vol. 222, pp. 273–279.

    Article  CAS  Google Scholar 

  • Sun, B.W., Yang, A.C., Feng, Y., et al., Temporal and Parental-Specific Expression of Imprinted Genes in a Newly Derived Chinese Human Embryonic Stem Cell Line and Embryoid Bodies, Hum. Mol. Genet., 2006, vol. 15, pp. 65–75.

    Article  PubMed  CAS  Google Scholar 

  • Szabo, P.E. and Mann, J.R., Biallelic Expression of Imprinted Genes in the Mouse Germ Line: Implications for Erasure, Establishment, and Mechanisms of Genomic Imprinting, Genes Devel., 1995, vol. 9, pp. 1857–1868.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, K. and Yamanaka, S., Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors, Cell, 2006, vol. 126, pp. 663–676.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, K., Tanabe, K., Ohnuki, V., et al., Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors, J. High Resolut. Chromatogr. Chromatogr. Commun., 2007, vol. 131, pp. 861–872.

    CAS  Google Scholar 

  • Takai, D., Gonzales, F.A., Tsai, Y.C., et al., Large Scale Mapping of Methylcytosines in CTCF-Binding Sites in the Human H19 Promoter and Aberrant Hypomethylation in Human Bladder Cancer, Hum. Mol. Genet., 2001, vol. 10, pp. 2619–2626.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, R.A., Cowin, P.A., Cunha, G.R., et al., Formation of Human Prostate Tissue from Embryomic Stem Cells, Nat. Methods, 2006, vol. 3, pp. 179–181.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, J.A., Kalishman, J., Golos, T.G., et al., Isolation of a Primate Embryonic Stem Cell Line, Proc. Natl. Acad. Sci. USA, 1995, vol. 92, pp. 7844–7848.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., et al., Embryonic Stem Cell Lines Derived from Human Blastocysts, Science, 1998, vol. 282, pp. 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, A., Wojtacha, D., Hewitt, Z., et al., Human Embryonic Stem Cells Passaged Using Enzymatic Methods Retain a Normal Karyotype and Express CD30, Cloning Stem Cells, 2008, vol. 10, no. 1, pp. 89–106.

    Article  PubMed  CAS  Google Scholar 

  • Ulaner, G.A., Vu, T.H., Li, T., et al., Loss of Imprinting of IGF2 and H19 in Osteosarcoma Is Accompanied by Reciprocal Methylation Changes of a CTCF-Binding Site, Hum. Mol. Genet., 2003, vol. 12, pp. 535–549.

    Article  PubMed  CAS  Google Scholar 

  • Vallier, L., Alexander, M., and Pedersen, R.A., Activin/Nodal and FGF Pathways Cooperate to Maintain Pluripotency of Human Embryonic Stem Cells, J. Cell Sci., 2005, vol. 118, pp. 4495–4509.

    Article  PubMed  CAS  Google Scholar 

  • Van Gurp, R.J., Oosterhuis, J.W., Kalscheuer, V., et al., Biallelic Expression of the H19 and IGF2 Genes in Human Testicular Germ Cell Tumors, J. Natl. Cancer Inst., 1994, vol. 86, pp. 1070–1075.

    Article  PubMed  Google Scholar 

  • Vrana, K.E., Hipp, J.D., Goss, A.M., et al., Nonhuman Primate Parthenogenetic Stem Cells, Proc. Natl. Acad. Sci. USA, 2003, vol. 100,suppl. 1, pp. 11911–11916.

    Article  PubMed  CAS  Google Scholar 

  • Wakayama, T., Perry, A.C., Zuccotti, M., et al., Full-Term Development of Mice from Enucleated Oocytes Injected with Cumulus Cell Nuclei, Nature, 1998, vol. 394, pp. 369–374.

    Article  PubMed  CAS  Google Scholar 

  • Wakayama, S., Ohta, H., Kishigami, S., et al., Establishment of Male and Female Nuclear Transfer Embryonic Stem Cell Lines from Different Mouse Strains and Tissues, Biol. Reprod., 2005, vol. 72, pp. 932–936.

    Article  PubMed  CAS  Google Scholar 

  • Weksberg, R., Smith, A.C., Squire, J., and Sadowski, P., Beckwith-Wiedemann Syndrome Demonstrates a Role for Epigenetic Control of Normal Development, Hum. Mol. Genet., 2003, vol. 12, pp. 61–68.

    Article  CAS  Google Scholar 

  • Westermann, F. and Schwab, M., Genetic Parameters of Neuroblastomas, Cancer Lett., 2002, vol. 184, pp. 127–147.

    Article  PubMed  CAS  Google Scholar 

  • Xu, C., Inokuma, M.S., Denham, J., et al., Feeder-Free Growth of Undifferentiated Human Embryonic Stem Cells, Nat. Biotechnol., 2001, vol. 19, no. 10, pp. 971–974.

    Article  PubMed  CAS  Google Scholar 

  • Xu, C., Jiang, J., Sottile, V., et al., Immortalized Fibroblast-Like Cells Derived from Human Embryonic Stem Cells Support Undifferentiated Cell Growth, Stem Cells, 2004, vol. 22, pp. 972–980.

    Article  PubMed  CAS  Google Scholar 

  • Xu, C., Rosler, E., Jiang, J., et al., Basic Fibroblast Growth Factor Supports Undifferentiated Human Embryonic Stem Cell Growth without Conditioned Medium, J. High Resolut. Chromatogr. Chromatogr. Commun., 2005, vol. 23, pp. 315–323.

    CAS  Google Scholar 

  • Xu, G.L., Bestor, T.H., Bourc’his, D., et al., Chromosome Instability and Immunodeficiency Syndrome Caused by Mutations in a DNA Methyltransferase Gene, Nature, 1999, vol. 402, pp. 187–191.

    Article  PubMed  CAS  Google Scholar 

  • Yu, J., Vodyanik, M., Smuga-Otoo, K., et al., Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells, Science, 2007, vol. 318, pp. 1917–1920.

    Article  PubMed  CAS  Google Scholar 

  • Zeng, X., Human Embryonic Stem Cells: Mechanisms to Escape Replicative Senescence?, Stem Cell Rev, 2007, vol. 3, pp. 270–279.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. F. Gordeeva.

Additional information

Original Russian Text © O.F. Gordeeva, Sh.M. Mitalipov, 2008, published in Ontogenez, 2008, Vol. 39, No. 6, pp. 405–419.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gordeeva, O.F., Mitalipov, S.M. Pluripotent stem cells: Maintenance of genetic and epigenetic stability and prospects of cell technologies. Russ J Dev Biol 39, 325–336 (2008). https://doi.org/10.1134/S1062360408060015

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062360408060015

Key words

Navigation