Telomeres, senescence, and hematopoietic stem cells (original) (raw)

References

• Abkowitz JL, Golinelli D, Harrison DE, Guttorp P (2000) In vivo kinetics of murine hemopoietic stem cells. Blood 96:3399–3405
  PubMed CAS Google Scholar
• Akimov SS, Ramezani A, Hawley TS, Hawley RG (2005) Bypass of senescence, immortalization, and transformation of human hematopoietic progenitor cells. Stem Cells 23:1423–1433
  PubMed CAS Google Scholar
• Akiyama M, Hoshi Y, Sakurai S, Yamada H, Yamada O, Mizoguchi H (1998) Changes of telomere length in children after hematopoietic stem cell transplantation. Bone Marrow Transplant 21:167–171
  PubMed CAS Google Scholar
• Akiyama M, Asai O, Kuraishi Y, Urashima M, Hoshi Y, Sakamaki H, Yabe H, Furukawa T, Yamada O, Mizoguchi H, Yamada H (2000) Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 25:441–447
  PubMed CAS Google Scholar
• Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, Greider CW, Harley CB (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 89:10114–10118
  PubMed CAS Google Scholar
• Allsopp RC, Cheshier S, Weissman IL (2001) Telomere shortening accompanies increased cell cycle activity during serial transplantation of hematopoietic stem cells. J Exp Med 193:917–924
  PubMed CAS Google Scholar
• Allsopp RC, Cheshier S, Weissman IL (2002) Telomerase activation and rejuvenation of telomere length in stimulated T cells derived from serially transplanted hematopoietic stem cells. J Exp Med 196:1427–1433
  PubMed CAS Google Scholar
• Allsopp RC, Morin GB, Horner JW, DePinho R, Harley CB, Weissman IL (2003a) Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells. Nat Med 9:369–371
  CAS Google Scholar
• Allsopp RC, Morin GB, DePinho R, Harley CB, Weissman IL (2003b) Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood 102:517–520
  Google Scholar
• Armanios M, Greider CW (2005) Telomerase and cancer stem cells. Cold Spring Harb Symp Quant Biol 70:205–208
  PubMed CAS Google Scholar
• Armstrong L, Saretzki G, Peters H, Wappler I, Evans J, Hole N, von Zglinicki T, Lako M (2005) Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage. Stem Cells 23:516–529
  PubMed CAS Google Scholar
• Artandi SE, Alson S, Tietze MK, Sharpless NE, Ye S, Greenberg RA, Castrillon DH, Horner JW, Weiler SR, Carrasco RD, DePinho RA (2002) Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc Natl Acad Sci USA 99:8191–8196
  PubMed CAS Google Scholar
• Asai A, Oshima Y, Yamamoto Y, Uochi TA, Kusaka H, Akinaga S, Yamashita Y, Pongracz K, Pruzan R, Wunder E, Piatyszek M, Li S, Chin AC, Harley CB, Gryaznov S (2003) A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res 63:3931–3939
  PubMed CAS Google Scholar
• Baerlocher GM, Lansdorp PM (2003) Telomere length measurements in leukocyte subsets by automated multicolor flow-FISH. Cytometry A 55:1–6
  PubMed Google Scholar
• Baerlocher GM, Rice K, Vulto I, Lansdorp PM (2006) Longitudinal data on telomere length in leukocytes from newborn baboons support a marked drop in stem cell turnover around 1 year of age. Aging Cell 6:121–123
  PubMed Google Scholar
• Ball SE, Gibson FM, Rizzo S, Tooze JA, Marsh JC, Gordon-Smith EC (1998) Progressive telomere shortening in aplastic anemia. Blood 91:3582–3592
  PubMed CAS Google Scholar
• Beausejour CM, Campisi J (2006) Ageing: balancing regeneration and cancer. Nature 443:404–405
  PubMed CAS Google Scholar
• Bhatia M, Wang J, Kapp U, Bonnet D, Dick JE (1997) Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci USA 94:5320–5325
  PubMed CAS Google Scholar
• Blackburn EH (2001) Switching and signaling at the telomere. Cell 106:661–673
  PubMed CAS Google Scholar
• Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91:25–34
  PubMed CAS Google Scholar
• Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352
  PubMed CAS Google Scholar
• Broccoli D, Young JW, de Lange T (1995) Telomerase activity in normal and malignant hematopoietic cells. Proc Natl Acad Sci USA 92:9082–9086
  PubMed CAS Google Scholar
• Brummendorf TH, Rufer N, Baerlocher GM, Roosnek E, Lansdorp PM (2001a) Limited telomere shortening in hematopoietic stem cells after transplantation. Ann Acad Sci 938:1–8
  CAS Google Scholar
• Brummendorf TH, Maciejewski JP, Mak J, Young NS, Lansdorp PM (2001b) Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood 97:895–900
  CAS Google Scholar
• Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120:513–522
  PubMed CAS Google Scholar
• Cao Y, Li H, Deb S, Liu JP (2002) TERT regulates cell survival independent of telomerase enzymatic activity. Oncogene 21:3130–3138
  PubMed CAS Google Scholar
• Carlesso N, Aster JC, Sklar J, Scadden DT (1999) Notch1-induced delay of human hematopoietic progenitor cell differentiation is associated with altered cell cycle kinetics. Blood 93:838–848
  PubMed CAS Google Scholar
• Cech TR (2004) Beginning to understand the end of the chromosome. Cell 116:273–279
  PubMed CAS Google Scholar
• Chiu CP, Dragowska W, Kim NW, Vaziri H, Yui J, Thomas TE, Harley CB, Lansdorp PM (1996) Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14:239–248
  PubMed CAS Google Scholar
• Choudhury AR, Ju Z, Djojosubroto MW, Schienke A, Lechel A, Schaetzlein S, Jiang H, Stepczynska A, Wang C, Buer J, Lee HW, von Zglinicki T, Ganser A, Schirmacher P, Nakauchi H, Rudolph KL (2007) Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet 39:99–105
  PubMed CAS Google Scholar
• Collins K, Mitchell JR (2002) Telomerase in the human organism. Oncogene 21:564–579
  PubMed CAS Google Scholar
• Collins CJ, Sedivy JM (2003) Involvement of the INK4a/Arf gene locus in senescence. Aging Cell 2:145–150
  PubMed CAS Google Scholar
• Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A (2003) Protein carbonylation in human diseases. Trends Mol Med 9:169–176
  PubMed CAS Google Scholar
• Damm K, Hemmann U, Garin-Chesa P, Hauel N, Kauffmann I, Priepke H, Niestroj C, Daiber C, Enenkel B, Guilliard B, Lauritsch I, Muller E, Pascolo E, Sauter G, Pantic M, Martens UM, Wenz C, Lingner J, Kraut N, Rettig WJ, Schnapp A (2001) A highly selective telomerase inhibitor limiting human cancer cell proliferation. EMBO J 20:6958–6968
  PubMed CAS Google Scholar
• Dikmen ZG, Gellert GC, Jackson S, Gryaznov S, Tressler R, Dogan P, Wright WE, Shay JW (2005) In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor. Cancer Res 65:7866–7873
  PubMed CAS Google Scholar
• Djojosubroto MW, Chin AC, Go N, Schaetzlein S, Manns MP, Gryaznov S, Harley CB, Rudolph KL (2005) Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma. Hepatology 42:1127–1136
  PubMed CAS Google Scholar
• dDokal I, Vulliamy T (2003) Dyskeratosis congenita: its link to telomerase and aplastic anaemia. Blood Rev 17:217–225
  PubMed Google Scholar
• El-Daly H, Kull M, Zimmermann S, Pantic M, Waller CF, Martens UM (2005) Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532. Blood 105:1742–1749
  PubMed CAS Google Scholar
• Elwood NJ, Jiang XR, Chiu CP, Lebkowski JS, Smith CA (2004) Enhanced long-term survival, but no increase in replicative capacity, following retroviral transduction of human cord blood CD34+ cells with human telomerase reverse transcriptase. Haematologica 89:377–378
  PubMed Google Scholar
• Engelhardt M, Kumar R, Albanell J, Pettengell R, Han W, Moore MA (1997) Telomerase regulation, cell cycle, and telomere stability in primitive hematopoietic cells. Blood 90:182–193
  PubMed CAS Google Scholar
• Fogarty PF, Yamaguchi H, Wiestner A, Baerlocher GM, Sloand E, Zeng WS, Read EJ, Lansdorp PM, Young NS (2003) Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA. Lancet 362:1628–1630
  PubMed CAS Google Scholar
• Folini M, Brambilla C, Villa R, Gandellini P, Vignati S, Paduano F, Daidone MG, Zaffaroni N (2005) Antisense oligonucleotide-mediated inhibition of hTERT, but not hTERC, induces rapid cell growth decline and apoptosis in the absence of telomere shortening in human prostate cancer cells. Eur J Cancer 41:624–634
  PubMed CAS Google Scholar
• Frenck RW Jr, Blackburn EH, Shannon KM (1998) The rate of telomere sequence loss in human leukocytes varies with age. Proc Natl Acad Sci USA 95:5607–5610
  PubMed CAS Google Scholar
• Gammaitoni L, Weisel KC, Gunetti M, Wu KD, Bruno S, Pinelli S, Bonati A, Aglietta M, Moore MA, Piacibello W (2004) Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication. Blood 103:4440–4448
  PubMed CAS Google Scholar
• Gellert GC, Dikmen ZG, Wright WE, Gryaznov S, Shay JW (2006) Effects of a novel telomerase inhibitor, GRN163L, in human breast cancer. Breast Cancer Res Treat 96:73–81
  PubMed CAS Google Scholar
• Glimm H, Eisterer W, Lee K, Cashman J, Holyoake TL, Nicolini F, Shultz LD, von Kalle C, Eaves CJ (2001) Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-beta2 microglobulin-null mice. J Clin Invest 107:199–206
  PubMed CAS Google Scholar
• Goldman F, Bouarich R, Kulkarni S, Freeman S, Du HY, Harrington L, Mason PJ, Londono-Vallejo A, Bessler M (2005) The effect of TERC haploinsufficiency on the inheritance of telomere length. Proc Natl Acad Sci USA 102:17119—17124
  PubMed CAS Google Scholar
• Gorbunova V, Seluanov A (2003) Telomerase as a growth-promoting factor. Cell Cycle 2:534–537
  PubMed CAS Google Scholar
• Greider CW, Blackburn EH (1989) A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 337:331–337
  PubMed CAS Google Scholar
• Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T(1999) Mammalian telomeres end in a large duplex loop. Cell 97:503–514
  PubMed CAS Google Scholar
• Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL, Knoll JH, Meyerson M, Weinberg RA (1999) Inhibition of telomerase limits the growth of human cancer cells. Nat Med 5:1164–1170
  PubMed CAS Google Scholar
• Hande MP, Samper E, Lansdorp P, Blasco MA (1999) Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. J Cell Biol 144:589–601
  PubMed CAS Google Scholar
• Hao LY, Armanios M, Strong MA, Karim B, Feldser DM, Huso D, Greider CW (2005) Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell 123:1121–1131
  PubMed CAS Google Scholar
• Harle-Bachor C, Boukamp P (1996) Telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma-derived skin keratinocytes. Proc Natl Acad Sci USA 93:6476–6481
  PubMed CAS Google Scholar
• Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460
  PubMed CAS Google Scholar
• Harley CB, Kim NW, Prowse KR, Weinrich SL, Hirsch KS, West MD, Bacchetti S, Hirte HW, Counter CM, Greider CW, et al (1994) Telomerase, cell immortality, and cancer. Cold Spring Harb Symp Quant Biol 59:307–315
  PubMed CAS Google Scholar
• Harrison D, Astle C (1982) Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure. J Exp Med 156:1767–1779
  PubMed CAS Google Scholar
• Harrison DE, Astle CM, Delaittre JA (1978) Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging. J Exp Med 147:1526–1531
  PubMed CAS Google Scholar
• Herbert B, Pitts AE, Baker SI, Hamilton SE, Wright WE, Shay JW, Corey DR (1999) Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Natl Acad Sci USA 96:14276–14281
  PubMed CAS Google Scholar
• Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311:1257
  PubMed CAS Google Scholar
• Herrera E, Samper E, Blasco MA (1999) Telomere shortening in mTR−/− embryos is associated with failure to close the neural tube. EMBO J 18:1172–1181
  PubMed CAS Google Scholar
• Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, Piatyszek MA, Shay JW, Ishioka S, Yamakido M (1995) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 155:3711–3715
  PubMed CAS Google Scholar
• Hooijberg E, Ruizendaal JJ, Snijders PJ, Kueter EW, Walboomers JM, Spits H (2000) Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase. J Immunol 165:4239–4245
  PubMed CAS Google Scholar
• Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, Nomiyama K, Hosokawa K, Sakurada K, Nakagata N, Ikeda Y, Mak TW, Suda T (2004) Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431:997–1002
  PubMed CAS Google Scholar
• Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR (2002) A stem cell molecular signature. Science 298:601–604
  Google Scholar
• Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443:421–426
  PubMed CAS Google Scholar
• Jaras M, Edqvist A, Rebetz J, Salford LG, Widegren B, Fan X (2006) Human short-term repopulating cells have enhanced telomerase reverse transcriptase expression. Blood 108:1084–1091
  PubMed Google Scholar
• Jaroscak J, Goltry K, Smith A, Waters-Pick B, Martin PL, Driscoll TA, Howrey R, Chao N, Douville J, Burhop S, Fu P, Kurtzberg J (2003) Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System. Blood 101:5061–5067
  PubMed CAS Google Scholar
• Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49
  PubMed CAS Google Scholar
• Ju Z, Jiang H, Jaworski M, Rathinam C, Gompf A, Klein C, Trumpp A, Rudolph KL (2007a) Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat Med 13:742–747
  PubMed CAS Google Scholar
• Ju Z, Choudhury AR, Rudolph KL (2007b) A dual role of p21 in stem cell aging. Ann N Y Acad Sci 1100:333–344
  PubMed CAS Google Scholar
• Kamminga LM, de Haan G (2006) Cellular memory and hematopoietic stem cell aging. Stem Cells 24:1143–1149
  PubMed CAS Google Scholar
• Keith WN (2004) From stem cells to cancer: balancing immortality and neoplasia. Oncogene 23:5092–5094
  PubMed CAS Google Scholar
• Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015
  PubMed CAS Google Scholar
• Kolquist KA, Ellisen LW, Counter CM, Meyerson M, Tan LK, Weinberg RA, Haber DA, Gerald WL (1998) Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nat Genet 19:182–186
  PubMed CAS Google Scholar
• Lansdorp PM (1995) Telomere length and proliferation potential of hematopoietic stem cells. J Cell Sci 108:1–6
  PubMed CAS Google Scholar
• Lansdorp PM, Dragowska W, Thomas TE, Little MT, Mayani H (1994) Age-related decline in proliferative potential of purified stem cell candidates. Blood Cells 20:376–380
  PubMed CAS Google Scholar
• Lansdorp PM, Poon S, Chavez E, Dragowska V, Zijlmans M, Bryan T, Reddel R, Egholm M, Bacchetti S, Martens U (1997) Telomeres in the haemopoietic system. Ciba Found Symp 211:209–222
  PubMed CAS Google Scholar
• Lee J, Kook H, Chung I, Kim H, Park M, Kim C, Nah J, Hwang T (1999) Telomere length changes in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 24:411–415
  PubMed CAS Google Scholar
• Lee JJ, Kook H, Chung IJ, Na JA, Park MR, Hwang TJ, Kwak JY, Sohn SK, Kim HJ (2001) Telomere length changes in patients with aplastic anaemia. Br J Haematol 112:1025–1030
  PubMed CAS Google Scholar
• Lessard J, Sauvageau G (2003) Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423:255–260
  PubMed CAS Google Scholar
• Li S, Ferguson MJ, Hawkins CJ, Smith C, Elwood NJ (2006) Human telomerase reverse transcriptase protects hematopoietic progenitor TF-1 cells from death and quiescence induced by cytokine withdrawal. Leukemia 20:1270–1278
  PubMed CAS Google Scholar
• Liu K, Schoonmaker MM, Levine BL, June CH, Hodes RJ, Weng NP (1999) Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes. Proc Natl Acad Sci USA 96:5147–5152
  PubMed CAS Google Scholar
• Liu Y, Snow BE, Hande MP, Yeung D, Erdmann NJ, Wakeham A, Itie A, Siderovski DP, Lansdorp PM, Robinson MO, Harrington L (2000) The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo. Curr Biol 10:1459–1462
  PubMed CAS Google Scholar
• Ly H, Calado RT, Allard P, Baerlocher GM, Lansdorp PM, Young NS, Parslow TG (2005) Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood 105:2332–2339
  PubMed CAS Google Scholar
• Maciejewski JP, Anderson S, Katevas P, Young NS (1994) Phenotypic and functional analysis of bone marrow progenitor cell compartment in bone marrow failure. Br J Haematol 87:227–234
  PubMed CAS Google Scholar
• Marrone A, Stevens D, Vulliamy T, Dokal I, Mason PJ (2004) Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufficiency. Blood 104:3936–3942
  PubMed CAS Google Scholar
• Marsh JC, Chang J, Testa NG, Hows JM, Dexter TM (1990) The hematopoietic defect in aplastic anemia assessed by long-term marrow culture. Blood 76:1748–1757
  PubMed CAS Google Scholar
• Martens UM, Zijlmans JM, Poon SS, Dragowska W, Yui J, Chavez EA, Ward RK, Lansdorp PM (1998) Short telomeres on human chromosome 17p. Nat Genet 18:76–80
  PubMed CAS Google Scholar
• Martens UM, Brass V, Sedlacek L, Pantic M, Exner C, Guo Y, Engelhardt M, Lansdorp PM, Waller CF, Lange W (2002) Telomere maintenance in human B lymphocytes. Br J Haematol 119:810–818
  PubMed CAS Google Scholar
• Marx J (2003) Cancer research. Mutant stem cells may seed cancer. Science 301:1308–1310
  PubMed CAS Google Scholar
• Maser RS, DePinho RA (2002) Connecting chromosomes, crisis, and cancer. Science 297:565–569
  PubMed CAS Google Scholar
• Massard C, Zermati Y, Pauleau AL, Larochette N, Metivier D, Sabatier L, Kroemer G, Soria JC (2006) hTERT: a novel endogenous inhibitor of the mitochondrial cell death pathway. Oncogene 25:4505–4514
  PubMed CAS Google Scholar
• Masutomi K, Yu EY, Khurts S, Ben-Porath I, Currier JL, Metz GB, Brooks MW, Kaneko S, Murakami S, DeCaprio JA, Weinberg RA, Stewart SA, Hahn WC (2003) Telomerase maintains telomere structure in normal human cells. Cell 114:241–253
  PubMed CAS Google Scholar
• Mitchell JR, Wood E, Collins K (1999) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402:551–555
  PubMed CAS Google Scholar
• Moore MA (2000) Umbilical cord blood: an expandable resource. J Clin Invest 105:855–856
  PubMed CAS Google Scholar
• Morrison SJ, Prowse KR, Ho P, Weissman IL (1996) Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5:207–216
  PubMed CAS Google Scholar
• Notaro R, Cimmino A, Tabarini D, Rotoli B, Luzzatto L (1997) In vivo telomere dynamics of human hematopoietic stem cells. Proc Natl Acad Sci USA 94:13782–13785
  PubMed CAS Google Scholar
• Nystrom T (2005) Role of oxidative carbonylation in protein quality control and senescence. EMBO J 24:1311–1317
  PubMed Google Scholar
• Ohyashiki JH, Sashida G, Tauchi T, Ohyashiki K (2002) Telomeres and telomerase in hematologic neoplasia. Oncogene 21:680–687
  PubMed CAS Google Scholar
• Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302–305
  PubMed CAS Google Scholar
• Pipes BL, Tsang T, Peng SX, Fiederlein R, Graham M, Harris DT (2006) Telomere length changes after umbilical cord blood transplant. Transfusion 46:1038–1043
  PubMed CAS Google Scholar
• Prasher JM, Lalai AS, Heijmans-Antonissen C, Ploemacher RE, Hoeijmakers JH, Touw IP, Niedernhofer LJ (2005) Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1−/− mice. EMBO J 24:861–871
  PubMed CAS Google Scholar
• Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science 298:597-600
  PubMed CAS Google Scholar
• Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–414
  PubMed CAS Google Scholar
• Robertson JD, Testa NG, Russell NH, Jackson G, Parker AN, Milligan DW, Stainer C, Chakrabarti S, Dougal M, Chopra R (2001) Accelerated telomere shortening following allogeneic transplantation is independent of the cell source and occurs within the first year post transplant. Bone Marrow Transplant 27:1283–1286
  PubMed CAS Google Scholar
• Rocci A, Ricca I, Dellacasa C, Longoni P, Compagno M, Francese R, Lobetti Bodoni C, Manzini P, Caracciolo D, Boccadoro M, Ferrero D, Ladetto M, Carlo-Stella C, Tarella C (2007) Long-term lymphoma survivors following high-dose chemotherapy and autograft: evidence of permanent telomere shortening in myeloid cells, associated with marked reduction of bone marrow hematopoietic stem cell reservoir. Exp Hematol 35:673–681
  PubMed CAS Google Scholar
• Roelofs H, de Pauw ES, Zwinderman AH, Opdam SM, Willemze R, Tanke HJ, Fibbe WE (2003) Homeostasis of telomere length rather than telomere shortening after allogeneic peripheral blood stem cell transplantation. Blood 101:358–362
  PubMed CAS Google Scholar
• Roth A, Yssel H, Pene J, Chavez EA, Schertzer M, Lansdorp PM, Spits H, Luiten RM (2003) Telomerase levels control the lifespan of human T lymphocytes. Blood 102:849–857
  PubMed Google Scholar
• Roth A, Baerlcher GM, Schertzer M, Chavez E, Duhrsen U, Lansdorp PM (2005) Telomere loss senescence and genetic instability in CD4+ T lymphocytes overexpressing hTERT. Blood 106:43–50
  PubMed Google Scholar
• Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96:701–712
  PubMed CAS Google Scholar
• Rufer N, Dragowska W, Thornbury G, Roosnek E, Lansdorp PM (1998) Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat Biotechnol 16:743–747
  PubMed CAS Google Scholar
• Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M, 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
  PubMed CAS Google Scholar
• Rufer N, Brummendorf TH, Chapuis B, Helg C, Lansdorp PM, Roosnek E (2001a) Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood 97:575–577
  CAS Google Scholar
• Rufer N, Migliaccio M, Antonchuk J, Humphries RK, Roosnek E, Lansdorp PM (2001b) Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential. Blood 98:597–603
  CAS Google Scholar
• Satija NK, Gurudutta GU, Sharma S, Afrin F, Gupta P, Verma YK, Singh VK, Tripathi RP (2007) Mesenchymal stem cells: molecular targets for tissue engineering. Stem Cells Dev 16:7–23
  PubMed CAS Google Scholar
• Sauvageau G, Thorsteinsdottir U, Eaves CJ, Lawrence HJ, Largman C, Lansdorp PM, Humphries RK (1995) Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev 9:1753–1765
  PubMed CAS Google Scholar
• Scopes J, Bagnara M, Gordon-Smith EC, Ball SE, Gibson FM (1994) Haemopoietic progenitor cells are reduced in aplastic anaemia. Br J Haematol 86:427–430
  Google Scholar
• Serakinci N, Guldberg P, Burns JS, Abdallah B, Schrodder H, Jensen T, Kassem M (2004) Adult human mesenchymal stem cell as a target for neoplastic transformation. Oncogene 23:5095–5098
  PubMed CAS Google Scholar
• Shepherd BE, Guttorp P, Lansdorp PM, Abkowitz JL (2004) Estimating human hematopoietic stem cell kinetics using granulocyte telomere lengths. Exp Hematol 32:1040–1050
  PubMed CAS Google Scholar
• Shi S, Gronthos S, Chen S, Reddi A, Counter CM, Robey PG, Wang CY (2002) Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol 20:587–591
  PubMed CAS Google Scholar
• Siminovitch L, Till JE, McCulloch EA (1964) Decline in colony-forming ability of marrow cells subjected to serial transplantation into irradiated mice. J Cell Physiol 64:23–31
  PubMed CAS Google Scholar
• Simonsen JL, Rosada C, Serakinci N, Justesen J, Stenderup K, Rattan SI, Jensen TG, 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
  PubMed CAS Google Scholar
• Slagboom PE, Droog S, Boomsma DI (1994) Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet 55:876–882
  PubMed CAS Google Scholar
• Son NH, Joyce B, Hieatt A, Chrest FJ, Yanovski J, Weng NP (2003) Stable telomere length and telomerase expression from naive to memory B-lymphocyte differentiation. Mech Ageing Dev 124:427–432
  PubMed CAS Google Scholar
• Stewart SA, Weinberg RA (2006) Telomeres: cancer to human aging. Annu Rev Cell Dev Biol 22:531–557
  PubMed CAS Google Scholar
• Tanavde VM, Malehorn MT, Lumkul R, Gao Z, Wingard J, Garrett ES, Civin CI (2002) Human stem-progenitor cells from neonatal cord blood have greater hematopoietic expansion capacity than those from mobilized adult blood. Exp Hematol 30:816–823
  PubMed CAS Google Scholar
• Terskikh AV, Miyamoto T, Chang C, Diatchenko L, Weissman IL (2003) Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood 102:94–101
  PubMed CAS Google Scholar
• Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147
  PubMed CAS Google Scholar
• Thornley I, Sutherland R, Wynn R, Nayar R, Sung L, Corpus G, Kiss T, Lipton J, Doyle J, Saunders F, Kamel-Reid S, Freedman M, Messner H (2002) Early hematopoietic reconstitution after clinical stem cell transplantation: evidence for stochastic stem cell behavior and limited acceleration in telomere loss. Blood 99:2387–2396
  PubMed CAS Google Scholar
• Traycoff CM, Kosak ST, Grigsby S, Srour EF (1995) Evaluation of ex vivo expansion potential of cord blood and bone marrow hematopoietic progenitor cells using cell tracking and limiting dilution analysis. Blood 85:2059–2068
  PubMed CAS Google Scholar
• Van Ziffle JA, Baerlocher GM, Lansdorp PM (2003) Telomere length in subpopulations of human hematopoietic cells. Stem Cells 21:654–660
  PubMed Google Scholar
• Vaziri H, Benchimol S (1998) Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol 8:279–282
  PubMed CAS Google Scholar
• Vaziri H, Schachter F, Uchida I, Wei L, Zhu X, Effros R, Cohen D, 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
• Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, 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
  PubMed CAS Google Scholar
• Verfaillie CM, Pera MF, Lansdorp PM (2002) Stem cells: hype and reality. Hematology Am Soc Hematol Educ Program 2002:369–391
  Google Scholar
• von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27:339–344
  Google Scholar
• Vulliamy T, Dokal I (2006) Dyskeratosis congenita. Semin Hematol 43:157–166
  PubMed CAS Google Scholar
• Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413:432–435
  PubMed CAS Google Scholar
• Vulliamy T, Marrone A, Dokal I, Mason PJ (2002) Association between aplastic anaemia and mutations in telomerase RNA. Lancet 359:2168–2170
  PubMed CAS Google Scholar
• Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, 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
  PubMed CAS Google Scholar
• Wang JC, Warner JK, Erdmann N, Lansdorp PM, Harrington L, Dick JE (2005) Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells. Proc Natl Acad Sci USA 102:14398–14403
  PubMed CAS Google Scholar
• Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239:197–201
  PubMed CAS Google Scholar
• Weng NP, Levine BL, June CH, Hodes RJ (1996) Regulated expression of telomerase activity in human T lymphocyte development and activation. J Exp Med 183:2471–2479
  PubMed CAS Google Scholar
• Weng NP, Hathcock KS, Hodes RJ (1998) Regulation of telomere length and telomerase in T and B cells: a mechanism for maintaining replicative potential. Immunity 9:151–157
  PubMed CAS Google Scholar
• Wright WE, Shay JW (2002) Historical claims and current interpretations of replicative aging. Nat Biotechnol 20:682–688
  PubMed CAS Google Scholar
• Wynn RF, Cross MA, Hatton C, Will AM, Lashford LS, Dexter TM, Testa NG (1998) Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. Lancet 351:178–181
  PubMed CAS Google Scholar
• Yamada O, Akiyama M, Kawauchi K, Adachi T, Yamada H, Kanda N, Aikawa E (2003) Overexpression of telomerase confers a survival advantage through suppression of TRF1 gene expression while maintaining differentiation characteristics in K562 cells. Cell Transplant 12:365–377
  PubMed Google Scholar
• Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS (2005) Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med 352:1413–1424
  PubMed CAS Google Scholar
• Yao CL, Feng YH, Lin XZ, Chu IM, Hsieh TB, Hwang SM (2006) Characterization of serum-free ex vivo-expanded hematopoietic stem cells derived from human umbilical cord blood CD133(+) cells. Stem Cells Dev 15:70–78
  PubMed CAS Google Scholar
• Yasumoto S, Kunimura C, Kikuchi K, Tahara H, Ohji H, Yamamoto H, Ide T, Utakoji T (1996) Telomerase activity in normal human epithelial cells. Oncogene 13:433–439
  PubMed CAS Google Scholar
• Yui J, Chiu CP, Lansdorp PM (1998) Telomerase activity in candidate stem cells from fetal liver and adult bone marrow. Blood 91:3255–3262
  PubMed CAS Google Scholar
• Zhang X, Mar V, Zhou W, Harrington L, Robinson MO (1999) Telomere shortening and apoptosis in telomerase-inhibited human tumor cells. Genes Dev 13:2388–2399
  PubMed CAS Google Scholar
• Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD (2005) Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 8:19–30
  PubMed CAS Google Scholar
• Zhao JQ, Glasspool RM, Hoare SF, Bilsland A, Szatmari I, Keith WN (2000) Activation of telomerase RNA gene promoter activity by NF-Y, Sp1, and the retinoblastoma protein and repression by Sp3. Neoplasia 2:531–539
  PubMed CAS Google Scholar
• Zhu X, Kumar R, Mandal M, Sharma N, Sharma HW, Dhingra U, Sokoloski JA, Hsiao R, Narayanan R (1996) Cell cycle-dependent modulation of telomerase activity in tumor cells. Proc Natl Acad Sci USA 93:6091–6095
  PubMed CAS Google Scholar
• Zhu J, Zhang Y, Joe GJ, Pompetti R, Emerson SG (2005) NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and promotes HSC self-renewal. Proc Natl Acad Sci USA 102:11728–11733
  PubMed CAS Google Scholar
• Zimmermann S, Martens UM (2007) Telomeres and telomerase as targets for cancer therapy. Cell Mol Lif Sci 64:906–921
  CAS Google Scholar
• Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF, Martens UM (2003) Lack of telomerase activity in human mesenchymal stem cells. Leukemia 17:1146–1149
  PubMed CAS Google Scholar
• Zimmermann S, Glaser S, Ketteler R, Waller CF, Klingmüller U, Martens UM (2004) Effects of telomerase modulation in human hematopoietic progenitor cells. Stem Cells 22:741–749
  PubMed CAS Google Scholar

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