GemC1 is a critical switch for neural stem cell generation in the postnatal brain.
Maria-Eleni LaliotiKonstantina KaplaniGeorgia LokkaTheodore GeorgomanolisChristina KyrousiWeilai DongAshley DunbarEvangelia ParlapaniEleni DamianidouNathalie SpasskyKristopher T KahleArgyris PapantonisZoi LygerouStavros TaravirasPublished in: Glia (2019)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- stem cells
- single cell
- neural stem cells
- endoplasmic reticulum stress
- endothelial cells
- type diabetes
- preterm infants
- signaling pathway
- gene expression
- genome wide
- dna damage
- cell therapy
- oxidative stress
- mesenchymal stem cells
- cell death
- transcription factor
- multiple sclerosis
- spinal cord injury
- white matter
- brain injury
- dna methylation
- neuropathic pain
- skeletal muscle
- genome wide association study
- resting state
- early life