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