| First Author | Szade K | Year | 2020 |
| Journal | EMBO Rep | Volume | 21 |
| Issue | 2 | Pages | e47895 |
| PubMed ID | 31885181 | Mgi Jnum | J:287924 |
| Mgi Id | MGI:6390452 | Doi | 10.15252/embr.201947895 |
| Citation | Szade K, et al. (2020) Heme oxygenase-1 deficiency triggers exhaustion of hematopoietic stem cells. EMBO Rep 21(2):e47895 |
| abstractText | 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 premature exhaustion on the transcriptional and functional level. HO-1(+/+) HSCs transplanted into HO-1(-/-) recipients exhaust their regenerative potential early and do not reconstitute secondary recipients. In turn, transplantation of HO-1(-/-) HSCs to the HO-1(+/+) recipients recovers the regenerative potential of HO-1(-/-) HSCs and reverses their transcriptional alterations. Thus, HSC-extrinsic activity of HO-1 prevents HSCs from premature exhaustion and may restore the function of aged HSCs. |
