Chronic stress induces neural stem cell quiescence in the hippocampus by repressing Ascl1 expression [CUT&Tag]

Here, using the 5-bromo-2′-deoxyuridine (BrdU) label-retaining assay, we found that chronic restraint stress (CRS) in adult mice promoted quiescence in hippocampal NSCs (i.e. radial-glial-like cells, RGLs). Long-term administration of the synthetic stress hormone agonist dexamethasone (Dex) to adult mice recapitulated the phenotype.

Moreover, pre-administration of the antagonist mifepristone (RU486) prevented RGLs from quiescence. At the cellular level, Dex induced reversible quiescence in hippocampal NSCs (HpNSCs) in a manner similar to the quiescence-promoting signal BMP4 in vitro. However, Dex and BMP4 regulated overlapping yet distinct NSC quiescence programs, with their co-regulation primarily being synergistic.