The journal EMBO Reports has published the paper Heme oxygenase-1 deficiency triggers exhaustion of hematopoietic stem cells co-authored by researchers from the Jagiellonian University Faculty of Biochemistry, Biophysics and Biotechnology, Faculty of Medicine, and Małopolska Centre of Biotechnology.
The abstract of the article reads: [The researchers] 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.
The paper was co-authored by researchers from the Jagiellonian University (Dr Agata Szade, Dr Krzysztof Szade, Dr Witold Nowak, Izabela Skulimowska, Maciej Cieśla, Dr Karolina Bukowska-Straková, Dr Neli Kachamakova-Trojanowska, Anna Kusienicka, Dr Jacek Kijowski, Prof. Alicja Józkowicz, and Prof. Józef Dulak), Stanford University, Medical University of Vienna, and European Molecular Biology Laboratory Heidelberg. Full version is available at embopress.org.
