Cyclin-Dependent Kinase Inhibitor p21 Controls Adult Neural Stem Cell Expansion by Regulating Sox2 Gene Expression

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• 作者：M. &Aacute ; ngeles Marqué ; s-Torrejó ; n¹ ; ² ; Eva Porlan¹ ; ² ; ⁶ ; Ana Banito³ ; ⁶ ; Esther Gó ; mez-Ibarlucea⁴ ; André ; s J. Lopez-Contreras⁵ ; Ó ; scar Fern&aacute ; ndez-Capetillo⁵ ; Anxo Vidal⁴ ; Jesú ; s Gil³ ; Josema Torres¹ ; ^{josema.torres@uv.es} ; Isabel Fariñ ; as¹ ; ² ; ^{isabel.farinas@uv.es}
• 刊名：Cell Stem Cell
• 出版年：2013
• 出版时间：3 January, 2013
• 年：2013
• 卷：12
• 期：1
• 页码：88-100
• 全文大小：2348 K

文摘

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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.