p63 调节嗅觉干细胞自我更新和分化。
p63 regulates olfactory stem cell self-renewal and differentiation.
机构信息
Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute & Functional Genomics Laboratory, University of California, Berkeley, CA 94720-3200, USA.
出版信息
Neuron. 2011 Dec 8;72(5):748-59. doi: 10.1016/j.neuron.2011.09.009.
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. However, the molecules and pathways regulating HBC self-renewal and differentiation are unknown. 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.
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节的极好模型。先前的研究已经确定水平基底细胞 (HBC) 是出生后嗅上皮的神经干细胞。然而，调节 HBC 自我更新和分化的分子和途径尚不清楚。在本研究中，我们证明转录因子 p63（一种已知调节其他上皮干细胞动力学的 p53 肿瘤抑制基因家族的成员）在 HBC 中高度富集。我们表明 p63 自主地需要维持嗅干细胞的更新，并且进一步表明 p63 可以抑制 HBC 分化。这些结果为体内嗅干细胞的遗传调控提供了重要的见解，并且更普遍地提供了理解干细胞自我更新和分化协调的途径。
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