Journal
GLIA
Volume 67, Issue 12, Pages 2360-2373Publisher
WILEY
DOI: 10.1002/glia.23690
Keywords
adult neurogenesis; congenital hydrocephalus; ependymal cells; GemC1; neural stem cells; neurosurgery; subventricular zone
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Funding
- Hellenic Foundation for Research and Innovation (HFRI)
- National Institutes of Health
- Simons Foundation
- March of Dimes (USA)
- March of Dimes Foundation
- Hellenic Foundation for Research and Innovation
- General Secretariat for Research and Technology
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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.
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