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Heme oxygenase-1 deficiency affects bone marrow niche and triggers premature exhaustion of hematopoietic stem cells.

Krzysztof Szade, Monika Żukowska, Agata Szade, Witold Norbert Nowak, Maciej Cieśla, Karolina Bukowska-Straková, Gunsagar Singh Gulati, Neli Kachamakova‐Trojanowska, Anna Kusienicka, Elisa Einwallner, Jacek Kijowski, Szymon Czauderna, Harald Esterbauer, Irving L. Weissman, Józef Dulak

bioRxiv (Cold Spring Harbor Laboratory) · 2018

Stem-cell exhaustion

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Abstract

While intrinsic changes in aging hematopoietic stem cells (HSCs) are well-characterized, it remains unclear how hematopoietic niche affects 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. RNA-sequencing shows that ECs and CARs from HO-1-deficient animals (HO-1-/-) produce less hematopoietic factors. Consequently, HSCs from young HO-1-/- animals lose quiescence and regenerative potential. Young HO-1-/- HSCs exhibit features of premature aging 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 aging and may restore the function of aged HSCs.

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Provenance

Source: OpenAlex
DOI: 10.1101/492850
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Fetched: 2026-10-06 MST

Cite this

APA

Szade, K., Żukowska, M., Szade, A., Nowak, W.N., Cieśla, M., Bukowska-Straková, K., Gulati, G.S., Kachamakova‐Trojanowska, N., Kusienicka, A., Einwallner, E., Kijowski, J., Czauderna, S., Esterbauer, H., Weissman, I.L., Dulak, J., & Józkowicz, A. (2018). Heme oxygenase-1 deficiency affects bone marrow niche and triggers premature exhaustion of hematopoietic stem cells. <em>bioRxiv (Cold Spring Harbor Laboratory)</em>. https://doi.org/10.1101/492850

Vancouver

Szade K, Żukowska M, Szade A, Nowak WN, Cieśla M, Bukowska-Straková K, et al. Heme oxygenase-1 deficiency affects bone marrow niche and triggers premature exhaustion of hematopoietic stem cells. bioRxiv (Cold Spring Harbor Laboratory). 2018. doi:10.1101/492850.

BibTeX

@unpublished{krzysztof2018Hemeox, title = {Heme oxygenase-1 deficiency affects bone marrow niche and triggers premature exhaustion of hematopoietic stem cells.}, author = {Krzysztof Szade and Monika Żukowska and Agata Szade and Witold Norbert Nowak and Maciej Cieśla and Karolina Bukowska-Straková and Gunsagar Singh Gulati and Neli Kachamakova‐Trojanowska and Anna Kusienicka and Elisa Einwallner and Jacek Kijowski and Szymon Czauderna and Harald Esterbauer and Irving L. Weissman and Józef Dulak and Alicja Józkowicz}, journal = {bioRxiv (Cold Spring Harbor Laboratory)}, year = {2018}, doi = {10.1101/492850}, }