Department of Physiology, School of Medicine, University of Patras, Patras, Greece.
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Glia. 2019 Dec;67(12):2360-2373. doi: 10.1002/glia.23690. Epub 2019 Jul 22.
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.
室下区（SVZ）是成年期持续存在神经发生的两个主要龛之一，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（NSC）。龛的另一个关键细胞成分是增殖后具有纤毛的室管膜细胞群体。这两种细胞类型都来源于在胚胎发生过程中被特化到每个谱系的放射状胶质细胞。我们在这里表明，编码 Geminin 卷曲螺旋结构域包含蛋白 1 的 GemC1 与人类和小鼠的先天性脑积水有关。我们的结果表明，GemC1 缺失会促使细胞向 NSC 表型发展，而牺牲了多纤毛室管膜细胞的生成。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 敲除细胞在多个基因座显示出改变的染色质组织，进一步支持 NSC 特性。总之，这些发现表明 GemC1 调节 NSC 生成和室管膜细胞分化之间的平衡，这对人类先天性脑积水的发病机制有影响。
