p53 REGULATES THE SELF-RENEWAL AND DIFFERENTIATION OF NEURAL PRECURSORS
p53 REGULATES THE SELF-RENEWAL AND DIFFERENTIATION OF NEURAL PRECURSORS
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DOI：
10.1016/j.neuroscience.2008.10.052
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发表时间：
2009-02-18
期刊：
影响因子：
3.3
通讯作者：
Silva, A.
中科院分区：
文献类型：
--
作者：
Armesilla-Diaz, A.;Bragado, P.;Silva, A.
在胚胎神经发生过程中，来自前脑室下区(SVZ)的干细胞的神经元不断地迁移到嗅球(OB)。然而，其他作者描述了OB中存在驻留干细胞的情况。在目前的工作中，我们报告了肿瘤抑制蛋白P53的缺失增加了神经球形成细胞的数量和13.5天胚胎OB来源的干细胞的增殖。有趣的是，p53基因敲除衍生的神经球的分化偏向于神经元前体，这表明p53在分化过程中发挥了作用。此外，我们还证明了在应对遗传毒性伤害时，p53在维持染色体稳定性方面的相关性。最后，我们的数据显示，神经球干细胞以一种不依赖于p53的方式高度抵抗长期表皮生长因子(EGF)和碱性成纤维细胞生长因子(BFGF)的剥夺，并保持其分化潜力。因此，这些数据表明，p53控制着胚胎小鼠嗅球干细胞的增殖、染色体稳定性和分化模式。(C)2009年IBRO。爱思唯尔有限公司出版。保留所有权利。
During embryo neurogenesis, neurons that originate from stem cells located in the forebrain subventricular zone (SVZ) continuously migrate to the olfactory bulb (OB). However, other authors describe the occurrence of resident stem cells in the OB. In the present work we report that the absence of tumor suppressor protein p53 increases the number of neurosphere-forming cells and the proliferation of stem cells derived from 13.5-day embryo OB. Interestingly, differentiation of p53 knockout-derived neurospheres was biased toward neuronal precursors, suggesting a role for p53 in the differentiation process. Moreover, we demonstrate the relevance of p53 in maintaining chromosomal stability in response to genotoxic insult. Finally, our data show that neurosphere stem cells are highly resistant to long-term epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) deprivation in a p53-independent fashion, and they preserve their differentiation potential. Thus, these data demonstrate that p53 controls the proliferation, chromosomal stability and differentiation pattern of embryonic mouse olfactory bulb stem cells. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.