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Stem cell function and maintenance – ends that matter: Role of telomeres and telomerase

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Abstract

Stem cell research holds a promise to treat and prevent age-related degenerative changes in humans. Literature is replete with studies showing that stem cell function declines with aging, especially in highly proliferative tissues/organs. Among others, telomerase and telomere damage is one of the intrinsic physical instigators that drive age-related degenerative changes. In this review we provide brief overview of telomerase-deficient aging affects in diverse stem cells populations. Furthermore, potential disease phenotypes associated with telomerase dysregulation in a specific stem cell population is also discussed in this review. Additionally, the role of telomerase in stem cell driven cancer is also briefly touched upon.

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References

  • Abdallah BM, Haack-Sorensen M, Fink T and Kassem M 2006 Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females. Bone 39 181–188

    Article  PubMed  Google Scholar 

  • Abdallah BM and Kassem M 2008 Human mesenchymal stem cells: from basic biology to clinical applications. Gene Ther. 15 109–116

    Article  PubMed  CAS  Google Scholar 

  • Abdallah BM and Kassem M 2009 The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: current status and future perspectives. J. Cell Physiol. 218 9–12

    Article  PubMed  CAS  Google Scholar 

  • Armstrong L, Lako M, Lincoln J, Cairns PM and Hole N 2000 mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cells. Mech. Dev. 97 109–116

    Article  PubMed  CAS  Google Scholar 

  • Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L and DePinho RA 2000 Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406 641–645

    Article  PubMed  CAS  Google Scholar 

  • Artegiani B and Calegari F 2012 Age-related cognitive decline: can neural stem cells help us? Aging 4 176–186

    PubMed  Google Scholar 

  • Balaban RS, Nemoto S and Finkel T 2005 Mitochondria, oxidants, and aging. Cell 120 483–495

    Article  PubMed  CAS  Google Scholar 

  • Ballas CB, Zielske SP and Gerson SL 2002 Adult bone marrow stem cells for cell and gene therapies: implications for greater use. J. Cell Biochem. Suppl. 38 20–28

    Article  PubMed  CAS  Google Scholar 

  • Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ and Bellantuono I 2004 Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22 675–682

    Article  PubMed  CAS  Google Scholar 

  • Bianco P, Riminucci M, Gronthos S and Robey PG 2001 Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19 180–192

    Article  PubMed  CAS  Google Scholar 

  • Blackburn EH 1984 Telomeres: do the ends justify the means? Cell 37 7–8

    Article  PubMed  CAS  Google Scholar 

  • Blackburn EH and Chiou SS 1981 Non-nucleosomal packaging of a tandemly repeated DNA sequence at termini of extrachromosomal DNA coding for rRNA in Tetrahymena. Proc. Natl. Acad. Sci. USA 78 2263–2267

    Article  PubMed  CAS  Google Scholar 

  • Blackburn EH and Gall JG 1978 A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J. Mol. Biol. 120 33–53

    Article  PubMed  CAS  Google Scholar 

  • Blasco MA 2005 Telomeres and human disease: ageing, cancer and beyond. Nat. Rev. Genet. 6 611–622

    Article  PubMed  CAS  Google Scholar 

  • Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA and Greider CW 1997 Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91 25–34

    Article  PubMed  CAS  Google Scholar 

  • Beausejour C 2011 Bone marrow-derived cells: the influence of aging and cellular senescence. Handbook Expe Pharmacol. 180 67–88

    Article  Google Scholar 

  • Campisi J 2005 Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120 513–522

    Article  PubMed  CAS  Google Scholar 

  • Chao H and Hirschi KK 2010 Hemato-vascular origins of endothelial progenitor cells? Microvasc. Res. 79 169–173

    Article  PubMed  CAS  Google Scholar 

  • Chen CW, Corselli M, Peault B and Huard J 2012 Human blood-vessel-derived stem cells for tissue repair and regeneration. J. Biomed. Biotechnol. 2012 597439

    PubMed  Google Scholar 

  • Chiu CP, Dragowska W, Kim NW, Vaziri H, Yui J, Thomas TE, Harley CB and Lansdorp PM 1996 Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14 239–248

    Article  PubMed  CAS  Google Scholar 

  • Cooke HJ and Smith BA 1986 Variability at the telomeres of the human X/Y pseudoautosomal region. Cold Spring Harb. Symp. Quant. Biol. 51 Pt 1 213–219

    Article  PubMed  CAS  Google Scholar 

  • Counter CM, Botelho FM, Wang P, Harley CB and Bacchetti S 1994 Stabilization of short telomeres and telomerase activity accompany immortalization of Epstein-Barr virus-transformed human B lymphocytes. J. Virol. 68 3410–3414

    PubMed  CAS  Google Scholar 

  • Darimont C, Avanti O, Tromvoukis Y, Vautravers-Leone P, Kurihara N, Roodman GD, Colgin LM, Tullberg-Reinert H, Pfeifer AM, Offord EA and Mace K 2002 SV40 T antigen and telomerase are required to obtain immortalized human adult bone cells without loss of the differentiated phenotype. Cell Growth Differ. 13 59–67

    PubMed  CAS  Google Scholar 

  • Darimont C, Zbinden I, Avanti O, Leone-Vautravers P, Giusti V, Burckhardt P, Pfeifer AM and Mace K 2003 Reconstitution of telomerase activity combined with HPV-E7 expression allow human preadipocytes to preserve their differentiation capacity after immortalization. Cell Death Differ. 10 1025–1031

    Article  PubMed  CAS  Google Scholar 

  • dda di FF, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, von ZT, Saretzki G, Carter NP and Jackson SP 2003 A DNA damage checkpoint response in telomere-initiated senescence. Nature 426 194–198

  • Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I and Pereira-Smith O 1995 A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. USA 92 9363–9367

    Article  PubMed  CAS  Google Scholar 

  • Djojosubroto MW, Choi YS, Lee HW and Rudolph KL 2003 Telomeres and telomerase in aging, regeneration and cancer. Mol. Cells 15 164–175

    PubMed  CAS  Google Scholar 

  • Effros RB, Allsopp R, Chiu CP, Hausner MA, Hirji K, Wang L, Harley CB, Villeponteau B, West MD and Giorgi JV 1996 Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. AIDS 10 F17–F22

    Article  PubMed  CAS  Google Scholar 

  • Endo T, Bryant SV and Gardiner DM 2004 A stepwise model system for limb regeneration. Dev. Biol. 270 135–145

    Article  PubMed  CAS  Google Scholar 

  • Espejel S, Klatt P, Menissier-de MJ, Martin-Caballero J, Flores JM, Taccioli G, de MG and Blasco MA 2004 Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs. J. Cell Biol. 167 627–638

  • Fehrer C and Lepperdinger G 2005 Mesenchymal stem cell aging. Exp. Gerontol. 40 926–930

    Article  PubMed  CAS  Google Scholar 

  • Ferron S, Mira H, Franco S, Cano-Jaimez M, Bellmunt E, Ramirez C, Farinas I and Blasco MA 2004 Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development 131 4059–4070

    Article  PubMed  CAS  Google Scholar 

  • Ferron SR, Marques-Torrejon MA, Mira H, Flores I, Taylor K, Blasco MA and Farinas I 2009 Telomere shortening in neural stem cells disrupts neuronal differentiation and neuritogenesis. J. Neurosci. 29 14394–14407

    Article  PubMed  CAS  Google Scholar 

  • Fibbe WE 2002 Mesenchymal stem cells. A potential source for skeletal repair. Ann. Rheum. Dis. 61 ii29–ii31

    PubMed  Google Scholar 

  • Flores I, Cayuela ML and Blasco MA 2005 Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309 1253–1256

    Article  PubMed  CAS  Google Scholar 

  • Forsyth NR, Wright WE and Shay JW 2002 Telomerase and differentiation in multicellular organisms: turn it off, turn it on, and turn it off again. Differentiation 69 188–197

    Article  PubMed  CAS  Google Scholar 

  • Freude S, Hettich MM, Schumann C, Stohr O, Koch L, Kohler C, Udelhoven M, Leeser U, et al. 2009 Neuronal IGF-1 resistance reduces Abeta accumulation and protects against premature death in a model of Alzheimer's disease. FASEB J. 23 3315–3324

    Article  PubMed  CAS  Google Scholar 

  • Gao J, Dennis JE, Muzic RF, Lundberg M and Caplan AI 2001 The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 169 12–20

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Suarez E, Samper E, Flores JM and Blasco MA 2000 Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat. Genet. 26 114–117

    Article  PubMed  CAS  Google Scholar 

  • Greenberg RA, Chin L, Femino A, Lee KH, Gottlieb GJ, Singer RH, Greider CW and DePinho RA 1999 Short dysfunctional telomeres impair tumorigenesis in the INK4a (delta2/3) cancer-prone mouse. Cell 97 515–525

    Article  PubMed  CAS  Google Scholar 

  • Greider CW and Blackburn EH 1985 Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43 405–413

    Article  PubMed  CAS  Google Scholar 

  • Hao LY, Armanios M, Strong MA, Karim B, Feldser DM, Huso D and Greider CW 2005 Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell 123 1121–1131

    Article  PubMed  CAS  Google Scholar 

  • Harada H, Mitsuyasu T, Toyono T and Toyoshima K 2002 Epithelial stem cells in teeth. Odontology 90 1–6

    Article  PubMed  Google Scholar 

  • Hayflick L and Moorheas PS 1961 The serial cultivation of human diploid cell strains. Exp. Cell Res. 25 585–621

    Article  PubMed  CAS  Google Scholar 

  • Herrera E, Martinez A and Blasco MA 2000 Impaired germinal center reaction in mice with short telomeres. EMBO J. 19 472–481

    Article  PubMed  CAS  Google Scholar 

  • Herrera E, Samper E, Martin-Caballero J, Flores JM, Lee HW and Blasco MA 1999 Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J. 18 2950–2960

    Article  PubMed  CAS  Google Scholar 

  • Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, Piatyszek MA, Shay JW, Ishioka S and Yamakido M 1995 Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155 3711–3715

    PubMed  CAS  Google Scholar 

  • Hodes RJ, Hathcock KS and Weng NP 2002 Telomeres in T and B cells. Nat. Rev. Immunol. 2 699–706

    Article  PubMed  CAS  Google Scholar 

  • Iwama H, Ohyashiki K, Ohyashiki JH, Hayashi S, Yahata N, Ando K, Toyama K, Hoshika A, Takasaki M, Mori M and Shay JW 1998 Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals. Hum. Genet. 102 397–402

    Article  PubMed  CAS  Google Scholar 

  • Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC, Sahin E, Kost-Alimova M, et al. 2011 Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469 102–106

    Article  PubMed  CAS  Google Scholar 

  • Ju Z, Jiang H, Jaworski M, Rathinam C, Gompf A, Klein C, Trumpp A and Rudolph KL 2007 Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat. Med. 13 742–747

    Article  PubMed  CAS  Google Scholar 

  • Ju Z and Rudolph KL 2006 Telomeres and telomerase in cancer stem cells. Eur. J. Cancer 42 1197–1203

    Article  PubMed  CAS  Google Scholar 

  • Jurgensen A, Mettler L, Volkov NI and Parwaresch R 1996 Proliferative activity of the endometrium throughout the menstrual cycle in infertile women with and without endometriosis. Fertil. Steril. 66 369–375

    PubMed  CAS  Google Scholar 

  • Kassem M, Abdallah BM, Yu Z, Ditzel N and Burns JS 2004 The use of hTERT-immortalized cells in tissue engineering. Cytotechnology 45 39–46

    Article  PubMed  Google Scholar 

  • Killick R, Scales G, Leroy K, Causevic M, Hooper C, Irvine EE, Choudhury AI, Drinkwater L, et al. 2009 Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice. Biochem. Biophys. Res. Commun. 386 257–262

    Article  PubMed  CAS  Google Scholar 

  • Kirwan M, Vulliamy T, Marrone A, Walne AJ, Beswick R, Hillmen P, Kelly R, Stewart A, et al. 2009 Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemia. Hum. Mutat. 30 1567–1573

    Article  PubMed  CAS  Google Scholar 

  • Knapowski J, Wieczorowska-Tobis K and Witowski J 2002 Pathophysiology of ageing. J. Physiol. Pharmacol. 53 135–146

    PubMed  CAS  Google Scholar 

  • Krtolica A and Campisi J 2003 Integrating epithelial cancer, aging stroma and cellular senescence. Adv. Gerontol. 11 109–116

    PubMed  CAS  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA and Dick JE 1994 A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367 645–648

    Article  PubMed  CAS  Google Scholar 

  • Lee HW, Blasco MA, Gottlieb GJ, Horner JW, Greider CW and DePinho RA 1998 Essential role of mouse telomerase in highly proliferative organs. Nature 392 569–574

    Article  PubMed  CAS  Google Scholar 

  • Lengauer C, Kinzler KW and Vogelstein B 1998 Genetic instabilities in human cancers. Nature 396 643–649

    Article  PubMed  CAS  Google Scholar 

  • Liu L, DiGirolamo CM, Navarro PA, Blasco MA and Keefe DL 2004 Telomerase deficiency impairs differentiation of mesenchymal stem cells. Exp. Cell Res. 294 1–8

    Article  PubMed  CAS  Google Scholar 

  • Martin JA and Buckwalter JA 2001 Telomere erosion and senescence in human articular cartilage chondrocytes. J. Gerontol. A Biol. Sci. Med. Sci. 56 B172–B179

    Article  PubMed  CAS  Google Scholar 

  • Martin-Rivera L, Herrera E, Albar JP and Blasco MA 1998 Expression of mouse telomerase catalytic subunit in embryos and adult tissues. Proc. Natl. Acad. Sci. U. S. A 95 10471–10476

    Article  PubMed  CAS  Google Scholar 

  • Montjovent MO, Burri N, Mark S, Federici E, Scaletta C, Zambelli PY, Hohlfeld P, Leyvraz PF, Applegate LL and Pioletti DP 2004 Fetal bone cells for tissue engineering. Bone 35 1323–1333

    Article  PubMed  CAS  Google Scholar 

  • Morrison SJ, Prowse KR, Ho P and Weissman IL 1996 Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5 207–216

    Article  PubMed  CAS  Google Scholar 

  • Parsch D, Brummendorf TH, Richter W and Fellenberg J 2002 Replicative aging of human articular chondrocytes during ex vivo expansion. Arthritis Rheum. 46 2911–2916

    Article  PubMed  CAS  Google Scholar 

  • Parsch D, Fellenberg J, Brummendorf TH, Eschlbeck AM and Richter W 2004 Telomere length and telomerase activity during expansion and differentiation of human mesenchymal stem cells and chondrocytes. J. Mol. Med. 82 49–55

    Article  PubMed  CAS  Google Scholar 

  • Pignolo RJ, Suda RK, McMillan EA, Shen J, Lee SH, Choi Y, Wright AC and Johnson FB 2008 Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis. Aging Cell 7 23–31

    Article  PubMed  CAS  Google Scholar 

  • Plentz RR, Caselitz M, Bleck JS, Gebel M, Flemming P, Kubicka S, Manns MP and Rudolph KL 2004 Hepatocellular telomere shortening correlates with chromosomal instability and the development of human hepatoma. Hepatology 40 80–86

    Article  PubMed  CAS  Google Scholar 

  • Plentz RR, Wiemann SU, Flemming P, Meier PN, Kubicka S, Kreipe H, Manns MP and Rudolph KL 2003 Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer. Gut 52 1304–1307

    Article  PubMed  CAS  Google Scholar 

  • Plunkett FJ, Franzese O, Belaramani LL, Fletcher JM, Gilmour KC, Sharifi R, Khan N, Hislop AD, et al. 2005 The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome. Mech. Ageing Dev. 126 855–865

    Article  PubMed  CAS  Google Scholar 

  • Rando TA 2006 Stem cells, ageing and the quest for immortality. Nature 441 1080–1086

    Article  PubMed  CAS  Google Scholar 

  • Richardson RM, Nguyen B, Holt SE, Broaddus WC and Fillmore HL 2007 Ectopic telomerase expression inhibits neuronal differentiation of NT2 neural progenitor cells. Neurosci. Lett. 421 168–172

    Article  PubMed  CAS  Google Scholar 

  • Rolyan H, Scheffold A, Heinrich A, Begus-Nahrmann Y, Langkopf BH, Holter SM, Vogt-Weisenhorn DM, Liss B, et al. 2011 Telomere shortening reduces Alzheimer's disease amyloid pathology in mice. Brain 134 2044–2056

    Article  PubMed  Google Scholar 

  • Rossi DJ, Jamieson CH and Weissman IL 2008 Stems cells and the pathways to aging and cancer. Cell 132 681–696

    Article  PubMed  CAS  Google Scholar 

  • Roth A, Vercauteren S, Sutherland HJ and Lansdorp PM 2003 Telomerase is limiting the growth of acute myeloid leukemia cells. Leukemia 17 2410–2417

    Article  PubMed  CAS  Google Scholar 

  • Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C and DePinho RA 1999 Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96 701–712

    Article  PubMed  CAS  Google Scholar 

  • Rudolph KL, Millard M, Bosenberg MW and DePinho RA 2001 Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat. Genet. 28 155–159

    Article  PubMed  CAS  Google Scholar 

  • Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M and Lansdorp PM 1999 Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J. Exp. Med. 190 157–167

    Article  PubMed  CAS  Google Scholar 

  • Saeed H, Abdallah BM, Ditzel N, Catala-Lehnen P, Qiu W, Amling M and Kassem M 2011 Telomerase-deficient mice exhibit bone loss due to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment. J. Bone Miner. Res

  • Sahin E and DePinho RA 2010 Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature 464 520–528

    Article  PubMed  CAS  Google Scholar 

  • Sarin KY, Cheung P, Gilison D, Lee E, Tennen RI, Wang E, Artandi MK, Oro AE and Artandi SE 2005 Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 436 1048–1052

    Article  PubMed  CAS  Google Scholar 

  • Satyanarayana A, Manns MP and Rudolph KL 2004 Telomeres and telomerase: a dual role in hepatocarcinogenesis. Hepatology 40 276–283

    Article  PubMed  CAS  Google Scholar 

  • Schieker M, Gulkan H, Austrup B, Neth P and Mutschler W 2004 Telomerase activity and telomere length of human mesenchymal stem cells. Changes during osteogenic differentiation. Orthopade 33 1373–1377

    Article  PubMed  CAS  Google Scholar 

  • Sharma HW, Sokoloski JA, Perez JR, Maltese JY, Sartorelli AC, Stein CA, Nichols G, Khaled Z, Telang NT and Narayanan R 1995 Differentiation of immortal cells inhibits telomerase activity. Proc. Natl. Acad. Sci. USA 92 12343–12346

    Article  PubMed  CAS  Google Scholar 

  • Sharpless NE and DePinho RA 2004 Telomeres, stem cells, senescence, and cancer. J. Clin. Invest. 113 160–168

    PubMed  CAS  Google Scholar 

  • Sharpless NE and DePinho RA 2007 How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol. 8 703–713

    Article  PubMed  CAS  Google Scholar 

  • Simonsen JL, Rosada C, Serakinci N, Justesen J, Stenderup K, Rattan SI, Jensen TG and Kassem M 2002 Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat. Biotechnol. 20 592–596

    Article  PubMed  CAS  Google Scholar 

  • Son NH, Murray S, Yanovski J, Hodes RJ and Weng N 2000 Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J. Immunol. 165 1191–1196

    PubMed  CAS  Google Scholar 

  • Song Z, Wang J, Guachalla LM, Terszowski G, Rodewald HR, Ju Z and Rudolph KL 2010 Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice. Blood 115 1481–1489

    Article  PubMed  Google Scholar 

  • Stenderup K, Justesen J, Clausen C and Kassem M 2003 Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33 919–926

    Article  PubMed  Google Scholar 

  • Stewart SA 2005 Telomere maintenance and tumorigenesis: an ‘ALT’ernative road. Curr. Mol. Med. 5 253–257

    Article  PubMed  CAS  Google Scholar 

  • T Miura, Y Katakura, K Yamamoto, N Uehara, T Tsuchiya, E H Kim and S Shirahata 2001 Neural stem cells lose telomerase activity upon differentiating into astrocytes. Cytotechnology 36 137–144

    Article  PubMed  CAS  Google Scholar 

  • Usselmann B, Newbold M, Morris AG and Nwokolo CU 2001 Telomerase activity and patient survival after surgery for gastric and oesophageal cancer. Eur. J. Gastroenterol. Hepatol. 13 903–908

    Article  PubMed  CAS  Google Scholar 

  • Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB and Lansdorp PM 1994 Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc. Natl. Acad. Sci. USA 91 9857–9860

    Article  PubMed  CAS  Google Scholar 

  • Vaziri H, Schachter F, Uchida I, Wei L, Zhu X, Effros R, Cohen D and Harley CB 1993 Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52 661–667

    PubMed  CAS  Google Scholar 

  • von ZT, Burkle A and Kirkwood TB 2001 Stress, DNA damage and ageing — an integrative approach. Exp. Gerontol. 36 1049–1062

  • Vulliamy T, Marrone A, Dokal I and Mason PJ 2002 Association between aplastic anaemia and mutations in telomerase RNA. Lancet 359 2168–2170

    Article  PubMed  CAS  Google Scholar 

  • Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ and Dokal I 2004 Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat. Genet. 36 447–449

    Article  PubMed  CAS  Google Scholar 

  • Wagner U, Pierer M, Wahle M, Moritz F, Kaltenhauser S and Hantzschel H 2004 Ex vivo homeostatic proliferation of CD4+ T cells in rheumatoid arthritis is dysregulated and driven by membrane-anchored TNF alpha. J. Immunol. 173 2825–2833

    PubMed  CAS  Google Scholar 

  • Weissman IL 2000 Stem cells: units of development, units of regeneration, and units in evolution. Cell 100 157–168

    Article  PubMed  CAS  Google Scholar 

  • Weng NP, Levine BL, June CH and Hodes RJ 1995 Human naive and memory T lymphocytes differ in telomeric length and replicative potential. Proc. Natl. Acad. Sci. USA 92 11091–11094

    Article  PubMed  CAS  Google Scholar 

  • Weng NP, Levine BL, June CH and Hodes RJ 1996 Regulated expression of telomerase activity in human T lymphocyte development and activation. J. Exp. Med. 183 2471–2479

    Article  PubMed  CAS  Google Scholar 

  • Wright WE and Shay JW 1992 The two-stage mechanism controlling cellular senescence and immortalization. Exp. Gerontol. 27 383–389

    Article  PubMed  CAS  Google Scholar 

  • Wu K, Higashi N, Hansen ER, Lund M, Bang K and Thestrup-Pedersen K 2000 Telomerase activity is increased and telomere length shortened in T cells from blood of patients with atopic dermatitis and psoriasis. J. Immunol. 165 4742–4747

    PubMed  CAS  Google Scholar 

  • Yudoh K, Matsuno H, Nakazawa F, Katayama R and Kimura T 2001 Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts. J. Bone Miner. Res. 16 1453–1464

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Khan D, Delling J and Tobiasch E 2012 Mechanisms underlying the osteo- and adipo-differentiation of human mesenchymal stem cells. Sci. World J. 2012 793823

    Google Scholar 

  • Zhao YM, Li JY, Lan JP, Lai XY, Luo Y, Sun J, Yu J, Zhu YY, Zeng FF, Zhou Q and Huang H 2008 Cell cycle dependent telomere regulation by telomerase in human bone marrow mesenchymal stem cells. Biochem. Biophys. Res. Commun. 369 1114–1119

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF and Martens UM 2003 Lack of telomerase activity in human mesenchymal stem cells. Leukemia 17 1146–1149

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Endocrinology, School of Medicine, Stanford University, Stanford, CA, USA

    Hamid Saeed

  2. Department of Bio-technology & Microbiology, Lahore College for Women University, Lahore, Pakistan

    Mehwish Iqtedar

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Correspondence to Hamid Saeed.

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Corresponding editor: Sudha Bhattacharya

[Saeed H and Iqtedar M 2013 Stem cell function and maintenance – ends that matter: Role of telomeres and telomerase. J. Biosci. 38 1–9] DOI 10.1007/s12038-013-9346-3

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Saeed, H., Iqtedar, M. Stem cell function and maintenance – ends that matter: Role of telomeres and telomerase. J Biosci 38, 641–649 (2013). https://doi.org/10.1007/s12038-013-9346-3

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