p63 regulates olfactory stem cell self-renewal and differentiation.
p63 regulates olfactory stem cell self-renewal and differentiation.
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DOI：
10.1016/j.neuron.2011.09.009
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发表时间：
2011-12-08
期刊：
影响因子：
16.2
通讯作者：
Ngai J
中科院分区：
文献类型：
--
作者：
Fletcher RB;Prasol MS;Estrada J;Baudhuin A;Vranizan K;Choi YG;Ngai J
嗅上皮是一种感觉神经上皮，支持成年神经发生和损伤后的组织再生，使其成为研究体内神经干细胞调控的良好模型。以往的研究已确定水平基底细胞（HBC）作为神经干细胞的出生后嗅上皮。然而，调节HBC自我更新和分化的分子和途径是未知的。在本研究中，我们证明，转录因子p63，已知在其他上皮细胞中调节干细胞动力学的p53肿瘤抑制基因家族的成员，是高度富集的HBCs。我们表明，p63是所需的细胞自主嗅觉干细胞更新，并进一步证明，p63的功能，抑制HBC分化。这些结果为嗅觉干细胞在体内的遗传调控提供了重要的见解，更普遍地说，为理解干细胞自我更新和分化的协调提供了一个切入点。
The olfactory epithelium is a sensory neuroepithelium that supports adult neurogenesis and tissue regeneration following injury, making it an excellent model for investigating neural stem cell regulation in vivo. Previous studies have identified the horizontal basal cell (HBC) as the neural stem cell of the postnatal olfactory epithelium. The molecules and pathways regulating HBC self-renewal and differentiation are unknown, however. In the present study we demonstrate that the transcription factor p63, a member of the p53 tumor suppressor gene family known to regulate stem cell dynamics in other epithelia, is highly enriched in HBCs. We show that p63 is required cell-autonomously for olfactory stem cell renewal and further demonstrate that p63 functions to repress HBC differentiation. These results provide critical insight into the genetic regulation of the olfactory stem cell in vivo, and more generally provide an entrée toward understanding the coordination of stem cell self-renewal and differentiation.
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