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Heme oxygenase‐1 deficiency triggers exhaustion of hematopoietic stem cells
Author(s) -
Szade Krzysztof,
Zukowska Monika,
Szade Agata,
Nowak Witold,
Skulimowska Izabella,
Ciesla Maciej,
BukowskaStrakova Karolina,
Gulati Gunsagar Singh,
KachamakovaTrojanowska Neli,
Kusienicka Anna,
Einwallner Elisa,
Kijowski Jacek,
Czauderna Szymon,
Esterbauer Harald,
Benes Vladimir,
L Weissman Irving,
Dulak Jozef,
Jozkowicz Alicja
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201947895
Subject(s) - haematopoiesis , stem cell , microbiology and biotechnology , biology , heme oxygenase , heme , hematopoietic stem cell , mesenchymal stem cell , immunology , biochemistry , enzyme
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.