Chromatin remodeling subunit BRM and valine regulate hematopoietic stem/progenitor cell function and self-renewal via intrinsic and extrinsic effects.

ABSTRACT: Little is known of hematopoietic stem (HSC) and progenitor (HPC) cell self-renewal. The role of Brahma (BRM), a chromatin remodeler, in HSC function is unknown. Bone marrow (BM) from Brm^-/- mice manifested increased numbers of long- and short-term HSCs, GMPs, and increased numbers and cycling of functional HPCs. However, increased Brm^-/- BM HSC numbers had decreased secondary and tertiary engraftment, suggesting BRM enhances HSC self-renewal. Valine was elevated in lineage negative Brm^-/- BM cells, linking intracellular valine with Brm expression. Valine enhanced HPC colony formation, replating of human cord blood (CB) HPC-derived colonies, mouse BM and human CB HPC survival in vitro, and ex vivo expansion of normal mouse BM HSCs and HPCs. Valine increased

SUBMITTER: Naidu SR 

PROVIDER: S-EPMC9212754 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature