1. Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB
- Author
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Chiara Rolando, Marta Milo, Verdon Taylor, Anna Engler, Robert Beattie, Sebastian Jessberger, Andrea Erni, Alice Grison, Paul J. Gokhale, and Thomas Wegleiter
- Subjects
Ribonuclease III ,0301 basic medicine ,Aging ,Neurogenesis ,Biology ,Hippocampal formation ,Hippocampus ,Mice ,03 medical and health sciences ,Neural Stem Cells ,Genetics ,Animals ,RNA, Messenger ,reproductive and urinary physiology ,Drosha ,Gliogenesis ,Mice, Knockout ,Base Sequence ,Multipotent Stem Cells ,Dentate gyrus ,Cell Differentiation ,Cell Biology ,Neural stem cell ,Adult Stem Cells ,NFI Transcription Factors ,Oligodendroglia ,030104 developmental biology ,nervous system ,NFIB ,Gene Knockdown Techniques ,Dentate Gyrus ,Cancer research ,biology.protein ,Molecular Medicine ,Neuroscience ,Gene Deletion ,Protein Binding ,Dicer - Abstract
Adult neural stem cells (NSCs) are defined by their inherent capacity to self-renew and give rise to neurons, astrocytes, and oligodendrocytes. In vivo, however, hippocampal NSCs do not generate oligodendrocytes for reasons that have remained enigmatic. Here, we report that deletion of Drosha in adult dentate gyrus NSCs activates oligodendrogenesis and reduces neurogenesis at the expense of gliogenesis. We further find that Drosha directly targets NFIB to repress its expression independently of Dicer and microRNAs. Knockdown of NFIB in Drosha-deficient hippocampal NSCs restores neurogenesis, suggesting that the Drosha/NFIB mechanism robustly prevents oligodendrocyte fate acquisition in vivo. Taken together, our findings establish that adult hippocampal NSCs inherently possess multilineage potential but that Drosha functions as a molecular barrier preventing oligodendrogenesis.
- Published
- 2016
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