GemC1 is a critical switch for neural stem cell generation in the postnatal brain
| Autor: | Zoi Lygerou, Stavros Taraviras, Georgia Lokka, Argyris Papantonis, Nathalie Spassky, Konstantina Kaplani, Eleni Damianidou, Christina Kyrousi, Evangelia Parlapani, Weilai Dong, Ashley Dunbar, Maria-Eleni Lalioti, Kristopher T. Kahle, Theodore Georgomanolis |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell type Ependymal Cell Neurogenesis Population Subventricular zone Cell Cycle Proteins Mice Transgenic 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Neural Stem Cells Pregnancy medicine Animals Humans education Cells Cultured Mice Knockout education.field_of_study biology Brain Geminin Neural stem cell nervous system diseases Cell biology Chromatin 030104 developmental biology medicine.anatomical_structure nervous system Neurology biology.protein Female 030217 neurology & neurosurgery Genes Switch |
| Zdroj: | GliaREFERENCES. 67(12) |
| ISSN: | 1098-1136 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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