New study provides novel insight into molecular mechanisms regulating neural stem cell fate (Taylor Lab)
Adult murine brains and their neural stem cells (NSCs) from the hippocampus are thoroughly guided to either renew themselves or differentiate into neurons and astrocytes. However, unlike NSCs from the subventricular zone, they do not generate oligodendrocytes in adulthood. In a recent publication in eLife by Pascal Forcella et al. (June 2024), Prof. Verdon Taylor’s team explored why this occurs and how NSC fate is regulated in the hippocampus at the RNA level and, more specifically, by the ribonuclease Drosha.
They discovered that scaffold attachment factor B (SAFB) plays a crucial role in blocking oligodendrocyte production to promote neuron generation. This study highlights that SAFB prevents the expression of the transcription factor nuclear factor I/B (NFIB) in NSCs by binding to specific sequences in the Nfib mRNA, enhancing its cleavage by the microprocessor protein Drosha. This interaction results in the post-transcriptional destabilization of Nfib mRNA, thus selectively regulating NSC fate. The research further demonstrates that increasing SAFB levels in NSCs inhibits oligodendrocyte formation, while conditional deletion of Safb leads to elevated NFIB expression and increased oligodendrocyte production in the adult hippocampus in vivo. These findings provide significant insights into the mechanisms controlling NSC differentiation and open new avenues for potential therapeutic strategies targeting neural repair and regeneration in neurological conditions.
Original Publication: https://elifesciences.org/articles/74940