Leading science, pioneering therapies
CRM Publications

Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression.

TitleCyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression.
Publication TypeJournal Article
Year of Publication2013
AuthorsM Marqués-Torrejón Á, Porlan E, Banito A, Gómez-Ibarlucea E, Lopez-Contreras AJ, Fernández-Capetillo O, Vidal A, Gil J, Torres J, Fariñas I
JournalCell Stem Cell
Date Published2013 Jan 3
KeywordsAdult Stem Cells, Animals, Cells, Cultured, Chromatin Immunoprecipitation, Cyclin-Dependent Kinase Inhibitor p21, Immunoblotting, Immunohistochemistry, Mice, Mice, Mutant Strains, Neural Stem Cells, Protein Binding, Reverse Transcriptase Polymerase Chain Reaction, SOXB1 Transcription Factors

In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis.

Alternate JournalCell Stem Cell
PubMed ID23260487
PubMed Central IDPMC3714747
Grant List11-0082 / / Worldwide Cancer Research / United Kingdom
210520 / / European Research Council / International
MC_U120085810 / / Medical Research Council / United Kingdom
/ / Cancer Research UK / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Howard Hughes Medical Institute / United States
Publication institute