Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 18 January 2001
Science 2 February 2001:
Vol. 291. no. 5505, pp. 868 - 871
DOI: 10.1126/science.1056780

Reports

Lack of Replicative Senescence in Cultured Rat Oligodendrocyte Precursor Cells

Dean G. Tang,*dagger Yasuhito M. Tokumoto, James A. Apperly, Alison C. Lloyd, Martin C. Raff

Most mammalian somatic cells are thought to have a limited proliferative capacity because they permanently stop dividing after a finite number of divisions in culture, a state termed replicative cell senescence. Here we show that most oligodendrocyte precursor cells purified from postnatal rat optic nerve can proliferate indefinitely in serum-free culture if prevented from differentiating; various cell cycle-inhibitory proteins increase, but the cells do not stop dividing. The cells maintain high telomerase activity and p53- and Rb-dependent cell cycle checkpoint responses, and serum or genotoxic drugs induce them to acquire a senescence-like phenotype. Our findings suggest that some normal rodent precursor cells have an unlimited proliferative capacity if cultured in conditions that avoid both differentiation and the activation of checkpoint responses that arrest the cell cycle.

MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
*   Present address: Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957, USA.

dagger    To whom correspondence should be addressed. E-mail: dtang{at}sprd1.mdacc.tmc.edu


Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Critical and Distinct Roles of p16 and Telomerase in Regulating the Proliferative Life Span of Normal Human Prostate Epithelial Progenitor Cells.
B. Bhatia, M. Jiang, M. Suraneni, L. Patrawala, M. Badeaux, R. Schneider-Broussard, A. S. Multani, C. R. Jeter, T. Calhoun-Davis, L. Hu, et al. (2008)
J. Biol. Chem. 283, 27957-27972
   Abstract »    Full Text »    PDF »
Constitutively Active Akt Induces Enhanced Myelination in the CNS.
A. I. Flores, S. P. Narayanan, E. N. Morse, H. E. Shick, X. Yin, G. Kidd, R. L. Avila, D. A. Kirschner, and W. B. Macklin (2008)
J. Neurosci. 28, 7174-7183
   Abstract »    Full Text »    PDF »
Myelin repair: the role of stem and precursor cells in multiple sclerosis.
S. Chandran, D. Hunt, A. Joannides, C. Zhao, A. Compston, and R. J.M Franklin (2008)
Phil Trans R Soc B 363, 171-183
   Abstract »    Full Text »    PDF »
Bone Morphogenetic Protein Signaling and Olig1/2 Interact to Regulate the Differentiation and Maturation of Adult Oligodendrocyte Precursor Cells.
X. Cheng, Y. Wang, Q. He, M. Qiu, S. R. Whittemore, and Q. Cao (2007)
Stem Cells 25, 3204-3214
   Abstract »    Full Text »    PDF »
A combined approach identifies a limited number of new thyroid hormone target genes in post-natal mouse cerebellum.
L. Quignodon, C. Grijota-Martinez, E. Compe, R. Guyot, N. Allioli, D. Laperriere, R. Walker, P. Meltzer, S. Mader, J. Samarut, et al. (2007)
J. Mol. Endocrinol. 39, 17-28
   Abstract »    Full Text »    PDF »
Resilience to Transformation and Inherent Genetic and Functional Stability of Adult Neural Stem Cells Ex vivo.
C. Foroni, R. Galli, B. Cipelletti, A. Caumo, S. Alberti, R. Fiocco, and A. Vescovi (2007)
Cancer Res. 67, 3725-3733
   Abstract »    Full Text »    PDF »
Autocrine Fibroblast Growth Factor 2 Signaling Is Critical for Self-Renewal of Human Multipotent Adipose-Derived Stem Cells.
L.-E. Zaragosi, G. Ailhaud, and C. Dani (2006)
Stem Cells 24, 2412-2419
   Abstract »    Full Text »    PDF »
Derivation and large-scale expansion of multipotent astroglial neural progenitors from adult human brain.
N. M. Walton, B. M. Sutter, H.-X. Chen, L.-J. Chang, S. N. Roper, B. Scheffler, and D. A. Steindler (2006)
Development 133, 3671-3681
   Abstract »    Full Text »    PDF »
Genes associated with adult axon regeneration promoted by olfactory ensheathing cells: a new role for matrix metalloproteinase 2..
E. Pastrana, M. T. Moreno-Flores, E. N. Gurzov, J. Avila, F. Wandosell, and J. Diaz-Nido (2006)
J. Neurosci. 26, 5347-5359
   Abstract »    Full Text »    PDF »
C5b-9 Terminal Complex Protects Oligodendrocytes from Apoptotic Cell Death by Inhibiting Caspase-8 Processing and Up-Regulating FLIP..
C. Cudrici, F. Niculescu, T. Jensen, E. Zafranskaia, M. Fosbrink, V. Rus, M. L. Shin, and H. Rus (2006)
J. Immunol. 176, 3173-3180
   Abstract »    Full Text »    PDF »
p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity.
T. E. Kippin, D. J. Martens, and D. van der Kooy (2005)
Genes & Dev. 19, 756-767
   Abstract »    Full Text »    PDF »
Cooperation between sonic hedgehog and fibroblast growth factor/MAPK signalling pathways in neocortical precursors.
N. Kessaris, F. Jamen, L. L. Rubin, and W. D. Richardson (2004)
Development 131, 1289-1298
   Abstract »    Full Text »    PDF »
Roles for p53 and p73 during oligodendrocyte development.
N. Billon, A. Terrinoni, C. Jolicoeur, A. McCarthy, W. D. Richardson, G. Melino, and M. Raff (2004)
Development 131, 1211-1220
   Abstract »    Full Text »    PDF »
Plasticity of marrow-derived stem cells.
E. L. Herzog, L. Chai, and D. S. Krause (2003)
Blood 102, 3483-3493
   Abstract »    Full Text »    PDF »
Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis.
J. Imitola, E. Y. Snyder, and S. J. Khoury (2003)
Physiol Genomics 14, 171-197
   Abstract »    Full Text »    PDF »
Dissecting the Contribution of p16INK4A and the Rb Family to the Ras Transformed Phenotype.
P. J. Mitchell, E. Perez-Nadales, D. S. Malcolm, and A. C. Lloyd (2003)
Mol. Cell. Biol. 23, 2530-2542
   Abstract »    Full Text »    PDF »
The significance of telomerase activation and cellular immortalization in human cancer.
R. F. Newbold (2002)
Mutagenesis 17, 539-550
   Abstract »    Full Text »    PDF »
Cyclin-Dependent Kinase-2 Controls Oligodendrocyte Progenitor Cell Cycle Progression and Is Downregulated in Adult Oligodendrocyte Progenitors.
S. Belachew, A. A. Aguirre, H. Wang, F. Vautier, X. Yuan, S. Anderson, M. Kirby, and V. Gallo (2002)
J. Neurosci. 22, 8553-8562
   Abstract »    Full Text »    PDF »
Replicative Senescence Revisited.
R. Marcotte and E. Wang (2002)
J. Gerontol. A Biol. Sci. Med. Sci. 57, B257-269
   Abstract »    Full Text »
Evidence That Arachidonate 15-Lipoxygenase 2 Is a Negative Cell Cycle Regulator in Normal Prostate Epithelial Cells.
S. Tang, B. Bhatia, C. J. Maldonado, P. Yang, R. A. Newman, J. Liu, D. Chandra, J. Traag, R. D. Klein, S. M. Fischer, et al. (2002)
J. Biol. Chem. 277, 16189-16201
   Abstract »    Full Text »    PDF »
Regulation of the Cell Cycle in Normal and Pathological Glia.
B. Stevens and R. D. Fields (2002)
Neuroscientist 8, 93-97
   Abstract »    PDF »
Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors.
D. Baas, C. Legrand, J. Samarut, and F. Flamant (2002)
PNAS
   Abstract »    Full Text »    PDF »
Stem Cells: Hype and Reality.
C. M. Verfaillie, M. F. Pera, and P. M. Lansdorp (2002)
Hematology 2002, 369-391
   Abstract »    Full Text »
C5b-9 Terminal Complement Complex Protects Oligodendrocytes from Death by Regulating Bad Through Phosphatidylinositol 3-Kinase/Akt Pathway.
L. Soane, H.-J. Cho, F. Niculescu, H. Rus, and M. L. Shin (2001)
J. Immunol. 167, 2305-2311
   Abstract »    Full Text »    PDF »
Stem Cells: A Journey into a New Frontier.
B. E. PETERSEN and N. TERADA (2001)
J. Am. Soc. Nephrol. 12, 1773-1780
   Full Text »    PDF »
Differential effects of p19Arf and p16Ink4a loss on senescence of murine bone marrow-derived preB cells and macrophages.
D. H. Randle, F. Zindy, C. J. Sherr, and M. F. Roussel (2001)
PNAS
   Abstract »    Full Text »    PDF »
Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors.
D. Baas, C. Legrand, J. Samarut, and F. Flamant (2002)
PNAS 99, 2907-2911
   Abstract »    Full Text »    PDF »
Differential effects of p19Arf and p16Ink4a loss on senescence of murine bone marrow-derived preB cells and macrophages.
D. H. Randle, F. Zindy, C. J. Sherr, and M. F. Roussel (2001)
PNAS 98, 9654-9659
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)