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RESEARCH PRODUCT

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

Eva PorlanAnxo VidalM. ÁNgeles Marqués-torrejónEsther Gómez-ibarluceaAna BanitoAndrés J. López-contrerasJosema TorresIsabel FariñasOscar Fernandez-capetilloJesús Gil

subject

Cèl·lules mare neuralsCyclin-Dependent Kinase Inhibitor p21Chromatin ImmunoprecipitationImmunoblottingArticle03 medical and health sciencesMice0302 clinical medicineSOX2Neural Stem CellsCyclin-dependent kinaseNeurosphereSubependymal zoneGeneticsExpressió genèticaAnimalsProgenitor cellCells Cultured030304 developmental biology0303 health sciencesbiologyCell growthReverse Transcriptase Polymerase Chain ReactionSOXB1 Transcription FactorsNeurogenesisCell BiologyImmunohistochemistryNeural stem cellMice Mutant Strains3. Good healthAdult Stem Cellsnervous systemCancer researchbiology.proteinMolecular Medicinebiological phenomena cell phenomena and immunity030217 neurology & neurosurgeryProtein Binding

description

Summary 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.

yearjournalcountryeditionlanguage
2012-03-24Cell stem cell
10.1016/j.stem.2012.12.001https://pubmed.ncbi.nlm.nih.gov/23260487