Redox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate.

ABSTRACT: Neural stem cell (NSC) maintenance and functions are regulated by reactive oxygen species (ROS). However, the mechanisms by which ROS control NSC behavior remain unclear. Here we report that ROS-dependent Igfbp2 signaling controls DNA repair pathways which balance NSC self-renewal and lineage commitment. Ncf1 or Igfbp2 deficiency constrains NSCs to a self-renewing state and prevents neurosphere formation. Ncf1-dependent oxidation of Igfbp2 promotes neurogenesis by NSCs in vitro and in vivo while repressing Brca1 DNA damage response genes and inducing DNA double-strand breaks (DDSBs). By contrast, Ncf1^-/- and Igfbp2^-/- NSCs favor the formation of oligodendrocytes in vitro and in vivo. Notably, transient repression of Brca1 DNA repair pathway genes induces DDSBs and is

SUBMITTER: Shahin WS 

PROVIDER: S-EPMC9883463 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature