Heme oxygenase‐1 deficiency triggers exhaustion of hematopoietic stem cells. (29th December 2019)

• Record Type: Journal Article
• Authors: Szade, Krzysztof; Zukowska, Monika; Szade, Agata; Nowak, Witold; Skulimowska, Izabella; Ciesla, Maciej; Bukowska‐Strakova, Karolina; Gulati, Gunsagar Singh; Kachamakova‐Trojanowska, Neli; Kusienicka, Anna; Einwallner, Elisa; Kijowski, Jacek; Czauderna, Szymon; Esterbauer, Harald; Benes, Vladimir; L Weissman, Irving; Dulak, Jozef; Jozkowicz, Alicja
• Is Part Of: EMBO reports. Volume 21:Number 2(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-12-29
• Subjects: aging -- bone marrow -- cxcl12‐abudant reticular cells -- endothelial cells -- niche; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201947895
• Languages: English
• ISSNs: 1469-221X

Abstract

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 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. Synopsis: The bone marrow niche harbors cell populations that constitutively express heme oxygenase 1 (HO‐1). HO‐1 regulates the niche and protects HSCs from exhaustion in a cell extrinsic manner. Heme oxygenase 1 (HO‐1) is a new factor in the bone marrow (BM) niche. The expression of HO‐1 in the BM niche decreases in aged animals. HSCs from young HO‐1 −/− mice resemble aged mice on the global transcriptome level. Extrinsic HO‐1 deficiency is linked to premature exhaustion of long‐term HSCs (LT‐HSCs). Abstract : The bone marrow niche harbors cell populations that constitutively express heme oxygenase 1 (HO‐1). HO‐1 regulates the niche and protects HSCs from exhaustion in a cell extrinsic manner.