Sox1 Maintains the Undifferentiated State of Cortical Neural Progenitor Cells via the Suppression of Prox1-Mediated Cell Cycle Exit and Neurogenesis
Sox1 Maintains the Undifferentiated State of Cortical Neural Progenitor Cells via the Suppression of Prox1-Mediated Cell Cycle Exit and Neurogenesis
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DOI：
10.1002/stem.554
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发表时间：
2011-01-01
期刊：
影响因子：
5.2
通讯作者：
Remboutsika, Eumorphia
中科院分区：
文献类型：
--
作者：
Elkouris, Maximilianos;Balaskas, Nikos;Remboutsika, Eumorphia
神经干/祖细胞通过持续的自我更新和抑制分化来维持其身份。在鸡的功能获得实验揭示了参与Sox 1 -3转录因子在未分化的神经祖细胞（NP）的身份的维护。然而，每个因素所采用的机制尚未得到解决。在这里，我们从野生型和Sox 1基因缺失的小鼠胚胎中获得皮质神经/干祖细胞，发现Sox 1在抑制神经源性细胞分裂中起着关键作用。Sox 1的缺失导致自我更新细胞的逐渐耗尽，增殖细胞的细胞周期延长，以及退出细胞周期的细胞数量显著增加。在增殖的NP细胞中，Sox 1通过一个与神经元相关的同源异型盒1（Prox 1）介导的途径来阻断细胞周期退出，从而导致体内和体外的神经元分化。因此，我们的研究结果表明，Sox 1调节的大小皮质NP池通过抑制Prox 1介导的神经源性细胞分裂。干细胞2011;29：89-98
Neural stem/progenitor cells maintain their identity via continuous self-renewal and suppression of differentiation. Gain-of-function experiments in the chick revealed an involvement for Sox1-3 transcription factors in the maintenance of the undifferentiated neural progenitor (NP) identity. However, the mechanism(s) employed by each factor has not been resolved. Here, we derived cortical neural/stem progenitor cells from wild-type and Sox1-null mouse embryos and found that Sox1 plays a key role in the suppression of neurogenic cell divisions. Loss of Sox1 leads to progressive depletion of self-renewing cells, elongation of the cell cycle of proliferating cells, and significant increase in the number of cells exiting the cell cycle. In proliferating NP cells, Sox1 acts via a prospero-related homeobox 1 (Prox1)-mediated pathway to block cell cycle exit that leads to neuronal differentiation in vivo and in vitro. Thus, our results demonstrate that Sox1 regulates the size of the cortical NP pool via suppression of Prox1-mediated neurogenic cell divisions. STEM CELLS 2011;29:89-98