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Does the reservoir for self-renewal stem from the ends?

Abstract

Stem cell research is a burgeoning field with an alluring potential for therapeutic intervention, and thus begs a critical understanding of the long-term consequences of stem cell replacement. Operationally, a stem cell may be defined as a rarely dividing cell with the capacity for self-renewal throughout the lifetime of the organism, and an ability to reconstitute its appropriate lineages via proliferation and differentiation. In many differentiated normal and cancer cell types, the maintenance of telomeres plays a pivotal role in their continued division potential. Taken together with the presence of the enzymatic activity responsible for telomere addition, telomerase, in several progenitor cell lineages, it is presumed that telomere maintenance will be critical for the replenishment of stem cells or their successors. The purpose of this review is to discuss the role of telomere length maintenance in self-renewal, and the consequent challenges and potential pitfalls to the manipulation of normal and cancer-derived stem cells.

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References

  • Allain JE, Dagher I, Mahieu-Caputo D, Loux N, Andreoletti M, Westerman K, Briand P, Franco D, Leboulch P and Weber A . (2002). Proc. Natl. Acad. Sci. USA, 99, 3639–3644.

  • Allsopp RC, Morin GB, DePinho R, Harley CB and Weissman IL . (2003a). Blood, 102, 517–520.

  • Allsopp RC, Morin GB, Horner JW, DePinho R, Harley CB and Weissman IL . (2003b). Nat. Med., 9, 369–371.

  • Allsopp RC and Weissman IL . (2002). Oncogene, 21, 3270–3273.

  • Artandi SE, Alson S, Tietze MK, Sharpless NE, Ye S, Greenberg RA, Castrillon DH, Horner JW, Weiler SR, Carrasco RD and DePinho RA . (2002). Proc. Natl. Acad. Sci. USA, 99, 8191–8196.

  • Baerlocher GM, Mak J, Tien T and Lansdorp PM . (2002). Cytometry, 47, 89–99.

  • Banfi A, Bianchi G, Notaro R, Luzzatto L, Cancedda R and Quarto R . (2002). Tissue Eng., 8, 901–910.

  • Bessler M, Wilson DB and Mason PJ . (2004). Curr. Opin. Pediatr., 16, 23–28.

  • Blackburn EH . (2001). Cell, 106, 661–673.

  • Blackburn EH and Gall J . (1978). J. Mol. Biol., 120, 33–53.

  • Blasco MA, Funk W, Villeponteau B and Greider CW . (1995). Science, 269, 1267–1270.

  • Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA and Greider CW . (1997). Cell, 91, 25–34.

  • Buchkovich KJ and Greider CW . (1996). Mol. Cell. Biol., 7, 1443–1454.

  • Carpenter MK, Rosler E and Rao MS . (2003). Cloning Stem Cells, 5, 79–88.

  • Chiu CP, Dragowska W, Kim NW, Vaziri H, Yui J, Thomas TE, Harley CB and Lansdorp PM . (1996). Stem Cells, 14, 239–248.

  • Cong YS, Wright WE and Shay JW . (2002). Microbiol. Mol. Biol. Rev., 66, 407–425 (table of contents).

  • 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 and Schnapp A . (2001). EMBO J., 20, 6958–6968.

  • Darwin C . (1898). The Descent of Man and Selection in Relation to Sex 1st edn. William Clowes and Sons: London.

    Google Scholar 

  • Erdmann N, Liu Y and Harrington L . (2004). Proc. Natl. Acad. Sci. USA, 101, 6080–6085.

  • Feng J, Funk WD, Wang S-S, Weinrich SL, Avilion AA, Chiu CP, Adams RR, Chang E, Allsopp RC, Yu J, Le S, West MD, Harley CB, Andrews WH, Greider CW and Villeponteau B . (1995). Science, 269, 1236–1241.

  • Fogarty PF, Yamaguchi H, Wiestner A, Baerlocher GM, Sloand E, Zeng WS, Read EJ, Lansdorp PM and Young NS . (2003). Lancet, 362, 1628–1630.

  • Gonzalez-Suarez E, Samper E, Ramirez A, Flores JM, Martin-Caballero J, Jorcano JL and Blasco MA . (2001). EMBO J., 20, 2619–2630.

  • Greenwood MJ and Lansdorp PM . (2003). Arch. Med. Res., 34, 489–495.

  • Greider CW . (1998a). Proc. Natl. Acad. Sci. USA, 95, 90–92.

  • Greider CW . (1998b). Curr. Biol., 8, R178–R181.

  • Greider CW and Blackburn EH . (1985). Cell, 43, 405–413.

  • Greider CW and Blackburn EH . (1987). Cell, 51, 887–898.

  • Greider CW and Blackburn EH . (1989). Nature, 337, 331–337.

  • Gronthos S, Zannettino AC, Hay SJ, Shi S, Graves SE, Kortesidis A and Simmons PJ . (2003). J. Cell Sci., 116, 1827–1835.

  • Hackett JA and Greider CW . (2002). Oncogene, 21, 619–626.

  • Harley CB . (1997). Ciba Found. Symp., 211, 129–139.

  • Harrington L and Robinson MO . (2002). Oncogene, 21, 592–597.

  • Harrington L, Zhou W, McPhail T, Oulton R, Yeung DS, Mar V, Bass MB and Robinson MO . (1997). Genes Dev., 11, 3109–3115.

  • Hemann MT, Rudolph KL, Strong MA, DePinho RA, Chin L and Greider CW . (2001). Mol. Cell. Biol., 12, 2023–2030.

  • Kilian A, Bowtell DD, Abud HE, Hime GR, Venter DJ, Keese PK, Duncan EL, Reddel RR and Jefferson RA . (1997). Hum. Mol. Genet., 6, 2011–2019.

  • Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PLC, Coviello GM, Wright WE, Weinrich SL and Shay JW . (1994). Science, 266, 2011–2015.

  • Klapper W, Shin T and Mattson MP . (2001). J. Neurosci. Res., 64, 252–260.

  • Kobune M, Kawano Y, Ito Y, Chiba H, Nakamura K, Tsuda H, Sasaki K, Dehari H, Uchida H, Honmou O, Takahashi S, Bizen A, Takimoto R, Matsunaga T, Kato J, Kato K, Houkin K, Niitsu Y and Hamada H . (2003). Exp. Hematol., 31, 715–722.

  • Lansdorp PM . (1998). Vox Sang, 74 (Suppl. 2), 91–94.

  • Lee HW, Blasco MA, Gottlieb GJ, Horner II JW, Greider CW and DePinho RA . (1998). Nature, 392, 569–574.

  • Lee KM, Nguyen C, Ulrich AB, Pour PM and Ouellette MM . (2003). Biochem. Biophys. Res. Commun., 301, 1038–1044.

  • Lendvay TS, Morris DK, Sah J, Balasubramanian B and Lundblad V . (1996). Genetics, 144, 1399–1412.

  • Limke TL, Cai J, Miura T, Rao MS and Mattson MP . (2003). Dev. Neurosci., 25, 257–272.

  • Lingner J, Hughes TR, Shevchenko A, Mann M, Lundblad V and Cech TR . (1997). Science, 276, 561–567.

  • Liu Y, Kha H, Ungrin M, Robinson MO and Harrington L . (2002). Proc. Natl. Acad. Sci. USA, 99, 3597–3602.

  • Liu Y, Snow BE, Hande MP, Yeung D, Erdmann NJ, Wakeham A, Itie A, Siderovski DP, Lansdorp PM, Robinson MO and Harrington L . (2000). Curr. Biol., 10, 1459–1462.

  • Lu C, Fu W and Mattson MP . (2001). Brain Res. Dev. Brain Res., 131, 167–171.

  • Mason PJ . (2003). BioEssays, 25, 126–133.

  • 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 and Hahn WC . (2003). Cell, 114, 241–253.

  • McEachern MJ and Blackburn EH . (1995). Nature, 376, 403–409.

  • Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, Caddle SD, Ziaugra L, Beijersbergen RL, Davidoff MJ, Liu Q, Bacchetti S, Haber DA and Weinberg RA . (1997). Cell, 90, 785–795.

  • Mihara K, Imai C, Coustan-Smith E, Dome JS, Dominici M, Vanin E and Campana D . (2003). Br. J. Haematol., 120, 846–849.

  • Miller MC and Collins K . (2000). Mol. Cell, 6, 827–837.

  • Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L, Helwig B, Beerenstrauch M, Abou-Easa K, Hildreth T, Troyer D and Medicetty S . (2003). Stem Cells, 21, 50–60.

  • Morales CP, Gandia KG, Ramirez RD, Wright WE, Shay JW and Spechler SJ . (2003). Gut, 52, 327–333.

  • Morales CP, Holt SE, Ouellette M, Kaur KJ, Yan Y, Wilson KS, White MA, Wright WE and Shay JW . (1999). Nat. Genet., 21, 115–118.

  • Morin GB . (1989). Cell, 59, 521–529.

  • Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB and Cech TR . (1997). Science, 277, 955–959.

  • Niida H, Shinkai Y, Hande MP, Matsumoto T, Takehara S, Tachibana M, Oshimura M, Lansdorp PM and Furuichi Y . (2000). Mol. Cell. Biol., 20, 4115–4127.

  • Parsch D, Fellenberg J, Brummendorf TH, Eschlbeck AM and Richter W . (2004). J. Mol. Med., 82, 49–55.

  • Pascolo E, Wenz C, Lingner J, Hauel N, Priepke H, Kauffmann I, Garin-Chesa P, Rettig WJ, Damm K and Schnapp A . (2002). J. Biol. Chem., 277, 15566–15572.

  • Poon SS, Martens UM, Ward RK and Lansdorp PM . (1999). Cytometry, 36, 267–278.

  • Prowse KR, Avilion AA and Greider CW . (1993). Proc. Natl. Acad. Sci. USA, 90, 1493–1497.

  • Reddel RR, Bryan TM, Colgin LM, Perrem KT and Yeager TR . (2001). Radiat. Res., 155, 194–200.

  • Riha K, McKnight TD, Griffing LR and Shippen DE . (2001). Science, 291, 1797–1800.

  • Riha K and Shippen DE . (2003). Chromosome Res., 11, 263–275.

  • Romero DP and Blackburn EH . (1991). Cell, 67, 343–353.

  • Rosler ES, Fisk GJ, Ares X, Irving J, Miura T, Rao MS and Carpenter MK . (2004). Dev. Dyn., 229, 259–274.

  • Roth A, Vercauteren S, Sutherland HJ and Lansdorp PM . (2003a). Leukemia, 17, 2410–2417.

  • Roth A, Yssel H, Pene J, Chavez EA, Schertzer M, Lansdorp PM, Spits H and Luiten RM . (2003b). Blood, 102, 849–857.

  • Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C and DePinho RA . (1999). Cell, 96, 701–712.

  • Rufer N, Dragowska W, Thornbury G, Roosnek E and Lansdorp PM . (1998). Nat. Biotechnol., 16, 743–747.

  • Ruggero D, Grisendi S, Piazza F, Rego E, Mari F, Rao PH, Cordon-Cardo C and Pandolfi PP . (2003). Science, 299, 259–262.

  • Samper E, Fernandez P, Eguia R, Martin-Rivera L, Bernad A, Blasco MA and Aracil M . (2002). Blood, 99, 2767–2775.

  • Shamblott MJ, Axelman J, Littlefield JW, Blumenthal PD, Huggins GR, Cui Y, Cheng L and Gearhart JD . (2001). Proc. Natl. Acad. Sci. USA, 98, 113–118.

  • Shippen-Lentz D and Blackburn EH . (1990). Science, 247, 546–552.

  • Singer MS and Gottschling DE . (1994). Science, 266, 404–409.

  • Truckenmiller ME, Vawter MP, Zhang P, Conejero-Goldberg C, Dillon-Carter O, Morales N, Cheadle C, Becker KG and Freed WJ . (2002). Exp. Neurol., 175, 318–337.

  • Ulaner GA, Hu JF, Vu TH, Giudice LC and Hoffman AR . (1998). Cancer Res., 58, 4168–4172.

  • Ulaner GA, Hu JF, Vu TH, Giudice LC and Hoffman AR . (2001). Int. J. Cancer, 91, 644–649.

  • Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB and Lansdorp PM . (1994). Proc. Natl. Acad. Sci. USA, 91, 9857–9860.

  • Vaziri H, Squire JA, Pandita TK, Bradley G, Kuba RM, Zhang H, Gulyas S, Hill RP, Nolan GP and Benchimol S . (1999). Mol. Cell. Biol., 19, 2373–2379.

  • Vrana KE, Hipp JD, Goss AM, McCool BA, Riddle DR, Walker SJ, Wettstein PJ, Studer LP, Tabar V, Cunniff K, Chapman K, Vilner L, West MD, Grant KA and Cibelli JB . (2003). Proc. Natl. Acad. Sci. USA, 100 (Suppl. 1), 11911–11916.

  • Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ and Dokal I . (2001a). Nature, 413, 432–435.

  • Vulliamy TJ, Knight SW, Mason PJ and Dokal I . (2001b). Blood Cells Mol. Dis., 27, 353–357.

  • Xiaoxue Y, Zhongqiang C, Zhaoqing G, Gengting D, Qingjun M and Shenwu W . (2004). Biochem. Biophys. Res. Commun., 315, 643–651.

  • Yuan X, Ishibashi S, Hatakeyama S, Saito M, Nakayama J, Nikaido R, Haruyama T, Watanabe Y, Iwata H, Iida M, Sugimura H, Yamada N and Ishikawa F . (1999). Genes Cells, 4, 563–572.

  • Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF and Martens UM . (2003). Leukemia, 17, 1146–1149.

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Acknowledgements

Where possible, several other relevant reviews on telomere homeostasis and stem cells have been referenced throughout. Unfortunately, space limitations have curtailed the inclusion of all primary literature. I thank Norman Iscove, John Dick, Guy Sauvageau, Rich Allsopp and Irv Weissman, and Jane Roskams for attempting to educate me about stem cells. The NIH (AG16629-04) provided financial support for the generation and analysis of mice deficient in mTert.

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Harrington, L. Does the reservoir for self-renewal stem from the ends?. Oncogene 23, 7283–7289 (2004). https://doi.org/10.1038/sj.onc.1207948

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Keywords

  • stem/progenitor cell
  • self-renewal
  • telomeres
  • telomerase

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