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Telomere and Telomerase for the Regulation of Stem Cells

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Regulatory Networks in Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Telomeres, guanine-rich tandem DNA repeats of chromosomal ends, provide chromosomal stability, and cellular replication causes their loss. In somatic cells, the activity of telomerase, a reverse transcriptase that can elongate telomeric repeats, is usually diminished after birth so that the telomere length is gradually shortened with cell divisions and triggers cellular senescence. In embryonic stem cells, telomerase is activated and maintains telomere length and cellular immortality. On the other hand, in adult stem cells, the level of telomerase activity is low and insufficient to maintain telomere length. Thus, even in stem cells, except for embryonic stem cells and cancer stem cells, telomere shortening occurs during replicative aging, possibly at a slower rate than that in normal somatic cells. In the past few years, the importance of telomere maintenance in human stem cells has been highlighted by the studies on dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis, a part of which are genetic disorders in the human telomerase component and are characterized by premature loss of tissue regeneration with stem cell dysfunction. The regulation of telomere length and telomerase activity is a complex and dynamic process that is tightly linked to cell cycle regulation in human stem cells. Here we review the role of telomeres and telomerase in human stem cells.

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References

  1. Blackburn EH. Switching and signaling at the telomere. Cell. 2001;106:661–73.

    PubMed  CAS  Google Scholar 

  2. Blackburn EH, Greider CW, Henderson E, Lee MS, Shampay J, Shippen-Lentz D. Recognition and elongation of telomeres by telomerase. Genome. 1989;31:553–60.

    PubMed  CAS  Google Scholar 

  3. Greider CW, Blackburn EH. The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell. 1987;51:887–98.

    PubMed  CAS  Google Scholar 

  4. Dhaene K, Van Marck E, Parwaresch R. Telomeres, telomerase and cancer: an up-date. Virchows Arch. 2000;437:1–16.

    PubMed  CAS  Google Scholar 

  5. Hiyama K, Hirai Y, Kyoizumi S, et al. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol. 1995;155:3711–5.

    PubMed  CAS  Google Scholar 

  6. Smogorzewska A, de Lange T. Regulation of telomerase by telomeric proteins. Annu Rev Biochem. 2004;73:177–208.

    PubMed  CAS  Google Scholar 

  7. Counter CM, Gupta J, Harley CB, Leber B, Bacchetti S. Telomerase activity in normal leukocytes and in hematologic malignancies. Blood. 1995;85:2315–20.

    PubMed  CAS  Google Scholar 

  8. Lee HW, Blasco MA, Gottlieb GJ, Horner JW, 2nd, Greider CW, DePinho RA. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998;392:569–74.

    PubMed  CAS  Google Scholar 

  9. Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A. 1994;91:9857–60.

    PubMed  CAS  Google Scholar 

  10. Allsopp RC, Cheshier S, Weissman IL. Telomere shortening accompanies increased cell cycle activity during serial transplantation of hematopoietic stem cells. J Exp Med. 2001;193:917–24.

    PubMed  CAS  Google Scholar 

  11. Allsopp RC, Morin GB, DePinho R, Harley CB, Weissman IL. Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood. 2003;102:517–20.

    PubMed  CAS  Google Scholar 

  12. Allsopp RC, Morin GB, Horner JW, DePinho R, Harley CB, Weissman IL. Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells. Nat Med. 2003;9:369–71.

    PubMed  CAS  Google Scholar 

  13. Hiyama E, Hiyama K, Tatsumoto N, Kodama T, Shay JW, Yokoyama T. Telomerase activity in human intestine. Int J Oncol. 1996;9:453–8.

    CAS  PubMed  Google Scholar 

  14. Flores I, Cayuela ML, Blasco MA. Effects of telomerase and telomere length on epidermal stem cell behavior. Science. 2005;309:1253–6.

    PubMed  CAS  Google Scholar 

  15. Ferron S, Mira H, Franco S, et al. Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development. 2004;131:4059–70.

    PubMed  CAS  Google Scholar 

  16. Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature. 2001;413:432–5.

    PubMed  CAS  Google Scholar 

  17. Wright WE, Shay JW. Telomere biology in aging and cancer. J Am Geriatr Soc. 2005;53:S292–4.

    PubMed  Google Scholar 

  18. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005;6:611–22.

    PubMed  CAS  Google Scholar 

  19. Collins K, Mitchell JR. Telomerase in the human organism. Oncogene. 2002;21:564–79.

    PubMed  CAS  Google Scholar 

  20. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100–10.

    PubMed  Google Scholar 

  21. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.

    PubMed  CAS  Google Scholar 

  22. Harley CB, Vaziri H, Counter CM, Allsopp RC. The telomere hypothesis of cellular aging. Exp Gerontol. 1992;27:375–82.

    PubMed  CAS  Google Scholar 

  23. Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC. Telomere reduction in human colorectal carcinoma and with ageing. Nature. 1990;346:866–8.

    PubMed  CAS  Google Scholar 

  24. Blasco MA. Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging. EMBO J. 2005;24:1095–103.

    PubMed  CAS  Google Scholar 

  25. Flores I, Benetti R, Blasco MA. Telomerase regulation and stem cell behaviour. Cur Op Cell Biol. 2006;18:254–60.

    CAS  Google Scholar 

  26. Garcia-Cao M, O’Sullivan R, Peters AH, Jenuwein T, Blasco MA. Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet. 2004;36:94–9.

    PubMed  CAS  Google Scholar 

  27. Gonzalo S, Garcia-Cao M, Fraga MF, et al. Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol. 2005;7:420–8.

    PubMed  CAS  Google Scholar 

  28. Muntoni A, Reddel RR. The first molecular details of ALT in human tumor cells. Hum Mol Genet. 2005;14 Spec No. 2: R191–6.

    PubMed  CAS  Google Scholar 

  29. Dunham MA, Neumann AA, Fasching CL, Reddel RR. Telomere maintenance by recombination in human cells. Nat Genet. 2000;26:447–50.

    PubMed  CAS  Google Scholar 

  30. Lundblad V. Telomere maintenance without telomerase. Oncogene. 2002;21:522–31.

    PubMed  CAS  Google Scholar 

  31. Hande MP, Samper E, Lansdorp P, Blasco MA. Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. J Cell Biol. 1999;144:589–601.

    PubMed  CAS  Google Scholar 

  32. Chang S, Khoo CM, Naylor ML, Maser RS, DePinho RA. Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression. Genes Dev. 2003;17:88–100.

    PubMed  CAS  Google Scholar 

  33. Niida H, Shinkai Y, Hande MP, et al. Telomere maintenance in telomerase-deficient mouse embryonic stem cells: characterization of an amplified telomeric DNA. Mol Cell Biol. 2000;20:4115–27.

    PubMed  CAS  Google Scholar 

  34. Herrera E, Martinez AC, Blasco MA. Impaired germinal center reaction in mice with short telomeres. EMBO J. 2000;19: 472–81.

    PubMed  CAS  Google Scholar 

  35. Blanco R, Munoz P, Flores JM, Klatt P, Blasco MA. Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis. Genes Dev. 2007;21:206–20.

    PubMed  CAS  Google Scholar 

  36. Wu L, Multani AS, He H, et al. Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell. 2006;126:49–62.

    PubMed  CAS  Google Scholar 

  37. Laud PR, Multani AS, Bailey SM, et al. Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes Dev. 2005;19:2560–70.

    PubMed  CAS  Google Scholar 

  38. Gonzalo S, Jaco I, Fraga MF, et al. DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol. 2006;8:416–24.

    PubMed  CAS  Google Scholar 

  39. Benetti R, Garcia-Cao M, Blasco MA. Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet. 2007;39:243–50.

    PubMed  CAS  Google Scholar 

  40. Benetti R, Gonzalo S, Jaco I, et al. Suv4-20 h deficiency results in telomere elongation and derepression of telomere recombination. J Cell Biol. 2007;178:925–36.

    PubMed  CAS  Google Scholar 

  41. Schoeftner S, Blasco MA. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol. 2008;10:228–36.

    PubMed  CAS  Google Scholar 

  42. Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW. Telomerase activity in human germline and embryonic tissues and cells. Dev Genet. 1996;18:173–9.

    PubMed  CAS  Google Scholar 

  43. Liu L, Bailey SM, Okuka M, et al. Telomere lengthening early in development. Nat Cell Biol. 2007;9:1436–41.

    PubMed  CAS  Google Scholar 

  44. Armstrong L, Saretzki G, Peters H, et al. Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage. Stem Cells. 2005;23:516–29.

    PubMed  CAS  Google Scholar 

  45. Lopatina NG, Poole JC, Saldanha SN, et al. Control mechanisms in the regulation of telomerase reverse transcriptase expression in differentiating human teratocarcinoma cells. Biochem Biophys Res Commun. 2003;306:650–9.

    PubMed  CAS  Google Scholar 

  46. Morton O, Williams N. First Dolly, now headless tadpoles. Science. 1997;278:798.

    PubMed  CAS  Google Scholar 

  47. Meerdo LN, Reed WA, White KL. Telomere-to-centromere ratio of bovine clones, embryos, gametes, fetal cells, and adult cells. Cloning Stem Cells. 2005;7:62–73.

    PubMed  CAS  Google Scholar 

  48. Serakinci N, Christensen R, Graakjaer J, et al. Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart. Exp Cell Res. 2007;313:1056–67.

    PubMed  CAS  Google Scholar 

  49. Graakjaer J, Christensen R, Kolvraa S, Serakinci N. Mesenchymal stem cells with high telomerase expression do not actively restore their chromosome arm specific telomere length pattern after exposure to ionizing radiation. BMC Mol Biol. 2007;8:49.

    PubMed  Google Scholar 

  50. Lansdorp PM. Lessons from mice without telomerase. J Cell Biol. 1997;139:309–12.

    PubMed  CAS  Google Scholar 

  51. Morrison SJ, Prowse KR, Ho P, Weissman IL. Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity. 1996;5:207–16.

    PubMed  CAS  Google Scholar 

  52. Vaziri H, Schachter F, Uchida I, et al. Loss of Telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet. 1993;52:661–7.

    PubMed  CAS  Google Scholar 

  53. Cooke HJ, Smith BA. Variability at the telomeres of the human X/Y pseudoautosomal region. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:213–9.

    PubMed  CAS  Google Scholar 

  54. Wynn RF, Cross MA, Hatton C, et al. Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. Lancet. 1998;351:178–81.

    PubMed  CAS  Google Scholar 

  55. Ohyashiki JH, Sashida G, Tauchi T, Ohyashiki K. Telomeres and telomerase in hematologic neoplasia. Oncogene. 2002;21: 680–7.

    PubMed  CAS  Google Scholar 

  56. Fehrer C, Lepperdinger G. Mesenchymal stem cell aging. Exp Gerontol. 2005;40:926–30.

    PubMed  CAS  Google Scholar 

  57. Yanada S, Ochi M, Kojima K, Sharman P, Yasunaga Y, Hiyama E. Possibility of selection of chondrogenic progenitor cells by telomere length in FGF-2-expanded mesenchymal stromal cells. Cell Prolif. 2006;39:575–84.

    PubMed  CAS  Google Scholar 

  58. Chiu CP, Dragowska W, Kim NW, et al. Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells. 1996;14:239–48.

    PubMed  CAS  Google Scholar 

  59. Harrington L. Does the reservoir for self-renewal stem from the ends? Oncogene. 2004;23:7283–9.

    PubMed  CAS  Google Scholar 

  60. Mason PJ, Wilson DB, Bessler M. Dyskeratosis congenita – a disease of dysfunctional telomere maintenance. Curr Mol Med. 2005;5:159–70.

    PubMed  CAS  Google Scholar 

  61. Ball SE, Gibson FM, Rizzo S, Tooze JA, Marsh JC, Gordon-Smith EC. Progressive telomere shortening in aplastic anemia. Blood. 1998;91:3582–92.

    PubMed  CAS  Google Scholar 

  62. Samper E, Fernandez P, Eguia R, et al. Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells. Blood. 2002;99:2767–75.

    PubMed  CAS  Google Scholar 

  63. Simonsen JL, Rosada C, Serakinci N, et al. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol. 2002;20:592–6.

    PubMed  CAS  Google Scholar 

  64. Liu L, Saldanha SN, Pate MS, Andrews LG, Tollefsbol TO. Epigenetic regulation of human telomerase reverse transcriptase promoter activity during cellular differentiation. Genes Chromosomes Cancer. 2004;41:26–37.

    PubMed  CAS  Google Scholar 

  65. Lee DH, Yang SC, Hong SJ, Chung BH, Kim IY. Telomerase: a potential marker of bladder transitional cell carcinoma in bladder washes. Clin Cancer Res. 1998;4:535–8.

    PubMed  CAS  Google Scholar 

  66. Rudolph KL, Chang S, Lee HW, et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell. 1999;96:701–12.

    PubMed  CAS  Google Scholar 

  67. Hao LY, Armanios M, Strong MA, et al. Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell. 2005;123:1121–31.

    PubMed  CAS  Google Scholar 

  68. Choudhury AR, Ju Z, Djojosubroto MW, et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet. 2007;39:99–105.

    PubMed  CAS  Google Scholar 

  69. Sarin KY, Cheung P, Gilison D, et al. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature. 2005;436:1048–52.

    PubMed  CAS  Google Scholar 

  70. Cayuela ML, Flores JM, Blasco MA. The telomerase RNA component Terc is required for the tumour-promoting effects of Tert overexpression. EMBO Rep. 2005;6:268–74.

    PubMed  CAS  Google Scholar 

  71. Ghazizadeh S, Taichman LB. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. EMBO J. 2001;20:1215–22.

    PubMed  CAS  Google Scholar 

  72. Levy V, Lindon C, Harfe BD, Morgan BA. Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev Cell. 2005;9:855–61.

    PubMed  CAS  Google Scholar 

  73. Ito M, Liu Y, Yang Z, et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med. 2005;11:1351–4.

    PubMed  CAS  Google Scholar 

  74. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA. Creation of human tumor cells with defined genetic elements. Nature. 1999;400:464–8.

    PubMed  CAS  Google Scholar 

  75. Hiyama E, Hiyama K. Clinical utility of telomerase in cancer. Oncogene. 2002;21:643–9.

    PubMed  CAS  Google Scholar 

  76. Hiyama E, Yokoyama T, Hiyama K, et al. Alteration of telomeric repeat length in adult and childhood solid neoplasias. Int J Oncol. 1995;6:13–6.

    PubMed  CAS  Google Scholar 

  77. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5.

    PubMed  CAS  Google Scholar 

  78. Hahn WC, Stewart SA, Brooks MW, et al. Inhibition of telomerase limits the growth of human cancer cells. Nat Med. 1999;5:1164–70.

    PubMed  CAS  Google Scholar 

  79. Greenwood MJ, Lansdorp PM. Telomeres, telomerase, and hematopoietic stem cell biology. Arch Med Res. 2003;34:489–95.

    PubMed  CAS  Google Scholar 

  80. Maciejewski JP, Risitano A. Hematopoietic stem cells in aplastic anemia. Arch Med Res. 2003;34:520–7.

    PubMed  CAS  Google Scholar 

  81. Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356:1317–26.

    PubMed  CAS  Google Scholar 

  82. Wright WE, Shay JW. Time, telomeres and tumours: is cellular senescence more than an anticancer mechanism? Trends Cell Biol. 1995;5:293–7.

    PubMed  CAS  Google Scholar 

  83. Bell DR, Van Zant G. Stem cells, aging, and cancer: inevitabilities and outcomes. Oncogene. 2004;23:7290–6.

    PubMed  CAS  Google Scholar 

  84. McEachern MJ, Krauskopf A, Blackburn EH. Telomeres and their control. Annu Rev Genet. 2000;34:331–58.

    PubMed  CAS  Google Scholar 

  85. de la Fuente J, Dokal I. Dyskeratosis congenita: advances in the understanding of the telomerase defect and the role of stem cell transplantation. Pediatr Transplant. 2007;11:584–94.

    PubMed  Google Scholar 

  86. Lee JJ, Kook H, Chung IJ, et al. Telomere length changes in patients with aplastic anaemia. Br J Haematol. 2001;112: 1025–30.

    PubMed  CAS  Google Scholar 

  87. Brummendorf TH, Maciejewski JP, Mak J, Young NS, Lansdorp PM. Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood. 2001;97:895–900.

    PubMed  CAS  Google Scholar 

  88. Vulliamy T, Marrone A, Dokal I, Mason PJ. Association between aplastic anaemia and mutations in telomerase RNA. Lancet. 2002;359:2168–70.

    PubMed  CAS  Google Scholar 

  89. McCulloch EA. Stem cells in normal and leukemic hemopoiesis (Henry Stratton Lecture, 1982). Blood. 1983;62:1–13.

    PubMed  CAS  Google Scholar 

  90. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.

    PubMed  CAS  Google Scholar 

  91. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–88.

    PubMed  CAS  Google Scholar 

  92. Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene. 2004;23:7274–82.

    PubMed  CAS  Google Scholar 

  93. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.

    PubMed  CAS  Google Scholar 

  94. Clarke MF, Fuller M. Stem cells and cancer: two faces of eve. Cell. 2006;124:1111–5.

    PubMed  CAS  Google Scholar 

  95. Brummendorf TH, Balabanov S. Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia. 2006;29:273–5.

    Google Scholar 

  96. Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF, Martens UM. Lack of telomerase activity in human mesenchymal stem cells. Leukemia. 2003;17:1146–9.

    PubMed  CAS  Google Scholar 

  97. Izadpanah R, Trygg C, Patel B, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem. 2006;99:1285–97.

    PubMed  CAS  Google Scholar 

  98. Sugihara M, Ohshima K, Nakamura H, et al. Decreased expression of telomerase-associated RNAs in the proliferation of stem cells in comparison with continuous expression in malignant tumors. Int J Oncol. 1999;15:1075–80.

    PubMed  CAS  Google Scholar 

  99. Wright LS, Prowse KR, Wallace K, Linskens MH, Svendsen CN. Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro. Exp Cell Res. 2006;312:2107–20.

    PubMed  CAS  Google Scholar 

  100. Moriscot C, de Fraipont F, Richard MJ, et al. Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Stem Cells. 2005;23:594–603.

    PubMed  CAS  Google Scholar 

  101. Dan YY, Riehle KJ, Lazaro C, et al. Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc Natl Acad Sci U S A. 2006;103:9912–7.

    PubMed  CAS  Google Scholar 

  102. Oh BK, Lee CH, Park C, Park YN. Telomerase regulation and progressive telomere shortening of rat hepatic stem-like epithelial cells during in vitro aging. Exp Cell Res. 2004;298:445–54.

    PubMed  CAS  Google Scholar 

  103. Hertzog RG. Ancestral telomere shortening: a countdown that will increase mean life span? Med Hypotheses. 2006;67:157–60.

    PubMed  CAS  Google Scholar 

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Hiyama, E., Hiyama, K. (2009). Telomere and Telomerase for the Regulation of Stem Cells. In: Rajasekhar, V.K., Vemuri, M.C. (eds) Regulatory Networks in Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-60327-227-8_11

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