Loss of ATF4 leads to functional aging-like attrition of adult hematopoietic stem cells.

ABSTRACT: Aging of hematopoietic stem cells (HSCs) directly contributes to dysfunction of hematopoietic and immune systems due to aging-associated alterations in HSC features. How the function of adult HSCs is regulated during aging so that relevant pathologic abnormalities may occur, however, remains incompletely understood. Here, we report that ATF4 deficiency provokes severe HSC defects with multifaceted aging-like phenotype via cell-autonomous mechanisms. ATF4 deletion caused expansion of phenotypical HSCs with functional attrition, characterized by defective repopulating and self-renewal capacities and myeloid bias. Moreover, the ATF4^−/− HSC defects were associated with elevated mitochondrial ROS production by targeting HIF1α. In addition, loss of ATF4 significantly del

SUBMITTER: Sun Y 

PROVIDER: S-EPMC8694622 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature