Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Cell Stem Cell |
Volume | 12 |
Issue number | 1 |
Pages (from-to) | 88-100 |
Number of pages | 13 |
ISSN | 1934-5909 |
DOIs | |
Publication status | Published - 3 Jan 2013 |
Externally published | Yes |
- Adult 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
Research areas
ID: 135740493