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

Authors

Weam S Shahin
Shima O Ebed MD, Lehigh Valley Health NetworkFollow
Scott R Tyler
Branko Miljkovic
Soon H Choi
Yulong Zhang
Weihong Zhou
Idil A Evans
Charles Yeaman
John F Engelhardt

Publication/Presentation Date

1-27-2023

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

Volume

14

Issue

1

First Page

444

Last Page

444

ISSN

2041-1723

Published In/Presented At

Shahin, W. S., Ebed, S. O., Tyler, S. R., Miljkovic, B., Choi, S. H., Zhang, Y., Zhou, W., Evans, I. A., Yeaman, C., & Engelhardt, J. F. (2023). Redox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate. Nature communications, 14(1), 444. https://doi.org/10.1038/s41467-023-36174-z

Disciplines

Medicine and Health Sciences

PubMedID

36707536

Department(s)

Fellows and Residents

Document Type

Article