Lack of replicative senescence in cultured rat oligodendrocyte precursor cells.
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.
Tang
D G
DG
MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
Tokumoto
Y M
YM
Apperly
J A
JA
Lloyd
A C
AC
Raff
M C
MC
D000818:Animals; D017209:Apoptosis; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence; D003260:Contact Inhibition; D016895:Culture Media, Serum-Free; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D009900:Optic Nerve / Q000166:cytology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D019098:Telomerase; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D016895:Culture Media, Serum-Free; D016213:Cyclins; D019384:Nucleic Acid Synthesis Inhibitors; D011506:Proteins; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D018844:Cyclin-Dependent Kinases; D019098:Telomerase; D018631:ras Proteins