Cohesin-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation.

ABSTRACT: Organism aging is characterized by increased inflammation and decreased stem cell function, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells (HSPCs) exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signaling, which increases chromatin accessibility in the vicinity of NF-κB target genes in response to inflammation. Rad21 is required for normal differentiation, but limits self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB-dependent manner. HSCs from aged mice fail to d

SUBMITTER: Chen Z 

PROVIDER: S-EPMC6314529 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature