GemC1 is a critical switch for neural stem cell generation in the postnatal brain
GemC1 is a critical switch for neural stem cell generation in the postnatal brain
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DOI：
10.1002/glia.23690
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发表时间：
2019-07-22
期刊：
影响因子：
6.2
通讯作者：
Taraviras, Stavros
中科院分区：
文献类型：
--
作者：
Lalioti, Maria-Eleni;Kaplani, Konstantina;Taraviras, Stavros
脑室下区（SVZ）是成年期神经发生持续存在的两个主要生态位之一，因为它保留了具有自我更新能力和多谱系潜能的神经干细胞（NSCs）。壁龛的另一个关键细胞组成部分是有丝分裂后多纤毛室管膜细胞群。这两种细胞类型都来源于放射状神经胶质细胞，在胚胎发生过程中，放射状神经胶质细胞被指定为每个谱系。我们发现GemC1编码Geminin卷曲螺旋结构域蛋白1，与人类和小鼠的先天性脑积水有关。我们的研究结果表明，GemC1缺陷驱动细胞向NSC表型，在多纤毛室管膜细胞的产生为代价。NSC数量的增加伴随着出生后SVZ中增殖和神经发生水平的增加。最后，GemC1基因敲除细胞在多个基因座显示改变的染色质组织，进一步支持NSC身份。总之，这些研究结果表明，GemC1调节NSC生成和室管膜细胞分化之间的平衡，与人类先天性脑积水的发病机制的影响。
The subventricular zone (SVZ) is one of two main niches where neurogenesis persists during adulthood, as it retains neural stem cells (NSCs) with self-renewal capacity and multi-lineage potency. Another critical cellular component of the niche is the population of postmitotic multiciliated ependymal cells. Both cell types are derived from radial glial cells that become specified to each lineage during embryogenesis. We show here that GemC1, encoding Geminin coiled-coil domain-containing protein 1, is associated with congenital hydrocephalus in humans and mice. Our results show that GemC1 deficiency drives cells toward a NSC phenotype, at the expense of multiciliated ependymal cell generation. The increased number of NSCs is accompanied by increased levels of proliferation and neurogenesis in the postnatal SVZ. Finally, GemC1-knockout cells display altered chromatin organization at multiple loci, further supporting a NSC identity. Together, these findings suggest that GemC1 regulates the balance between NSC generation and ependymal cell differentiation, with implications for the pathogenesis of human congenital hydrocephalus.