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.
Lack of Replicative Senescence in Cultured Rat Oligodendrocyte Precursor Cells
Dean G. Tang,*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
aftera finite number of divisions in culture, a state termed
replicativecell senescence. Here we show that most oligodendrocyte
precursorcells purified from postnatal rat optic nerve can proliferateindefinitely in serum-free culture if prevented from differentiating;various cell cycle-inhibitory proteins increase, but the cellsdo not
stop dividing. The cells maintain high telomerase activityand p53- and
Rb-dependent cell cycle checkpoint responses, andserum or genotoxic
drugs induce them to acquire a senescence-likephenotype. Our findings
suggest that some normal rodent precursorcells have an unlimited
proliferative capacity if cultured inconditions that avoid both
differentiation and the activationof 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.
To whom correspondence should be addressed.
E-mail: dtang{at}sprd1.mdacc.tmc.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
REPORTS
Nicole F. Mathon, Denise S. Malcolm, Marie C. Harrisingh, Lili Cheng, and Alison C. Lloyd (2 February 2001) Science291 (5505), 872.
[DOI: 10.1126/science.1056782] |Abstract »|Full Text »|PDF »|Supplemental Data »
PERSPECTIVES
Jerry W. Shay and Woodring E. Wright (2 February 2001) Science291 (5505), 839.
[DOI: 10.1126/science.1058546] |Summary »|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.
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 »
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.
Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors.