Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

Paper URL: Science Direct

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.

Key Findings

• Drosha regulates adult hippocampal stem cell maintenance

• Drosha inhibits oligodendrocytic differentiation of adult stem cells

• Drosha targets NFIB mRNA hairpin to inhibit expression and enable neurogenesis

• NFIB expression induces oligodendrocytic fate in adult hippocampal stem cells