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Publication : Genome integrity and neurogenesis of postnatal hippocampal neural stem/progenitor cells require a unique regulator Filia.

First Author  Li J Year  2020
Journal  Sci Adv Volume  6
Issue  44 PubMed ID  33115731
Mgi Jnum  J:306603 Mgi Id  MGI:6716977
Doi  10.1126/sciadv.aba0682 Citation  Li J, et al. (2020) Genome integrity and neurogenesis of postnatal hippocampal neural stem/progenitor cells require a unique regulator Filia. Sci Adv 6(44)
abstractText  Endogenous DNA double-strand breaks (DSBs) formation and repair in neural stem/progenitor cells (NSPCs) play fundamental roles in neurogenesis and neurodevelopmental disorders. NSPCs exhibit heterogeneity in terms of lineage fates and neurogenesis activity. Whether NSPCs also have heterogeneous regulations on DSB formation and repair to accommodate region-specific neurogenesis has not been explored. Here, we identified a regional regulator Filia, which is predominantly expressed in mouse hippocampal NSPCs after birth and regulates DNA DSB formation and repair. On one hand, Filia protects stalling replication forks and prevents the replication stress-associated DNA DSB formation. On the other hand, Filia facilitates the homologous recombination-mediated DNA DSB repair. Consequently, Filia(-/-) mice had impaired hippocampal NSPC proliferation and neurogenesis and were deficient in learning, memory, and mood regulations. Thus, our study provided the first proof of concept demonstrating the region-specific regulations of DSB formation and repair in subtypes of NSPCs.
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