Heme oxygenase-1 deficiency triggers exhaustion of hematopoietic stem cells.

ABSTRACT: While intrinsic changes in aging hematopoietic stem cells (HSCs) are well characterized, it remains unclear how extrinsic factors affect HSC aging. Here, we demonstrate that cells in the niche-endothelial cells (ECs) and CXCL12-abundant reticular cells (CARs)-highly express the heme-degrading enzyme, heme oxygenase 1 (HO-1), but then decrease its expression with age. HO-1-deficient animals (HO-1^-/- ) have altered numbers of ECs and CARs that produce less hematopoietic factors. HSCs co-cultured in vitro with HO-1^-/- mesenchymal stromal cells expand, but have altered kinetic of growth and differentiation of derived colonies. HSCs from young HO-1^-/- animals have reduced quiescence and regenerative potential. Young HO-1^-/- HSCs exhibit features of pr

SUBMITTER: Szade K 

PROVIDER: S-EPMC7001511 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature