Sex-dependent niche responses modulate steady-state and regenerative hematopoiesis.

Autor: Chaudhary R; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Smith JNP; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Tiwari R; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Klein BR; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Cordova BA; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Petroze F; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Richardson B; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Broncano AV; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Lee J; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio; Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio., Parthasarathy PB; Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio., De Carvalho KIL; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Cameron SJ; Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio., Lathia JD; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio; Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio., Goodman WA; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Cameron MJ; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio., Desai AB; Case Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio. Electronic address: Abd10@case.edu.
Jazyk: angličtina
Zdroj: Experimental hematology [Exp Hematol] 2024 Sep; Vol. 137, pp. 104247. Date of Electronic Publication: 2024 Jun 06.
DOI: 10.1016/j.exphem.2024.104247
Abstrakt: Hematopoietic stem cells (HSCs) adapt to organismal blood production needs by balancing self-renewal and differentiation, adjusting to physiological demands and external stimuli. Although sex differences have been implicated in differential hematopoietic function in males versus females, the mediators responsible for these effects require further study. Here, we characterized hematopoiesis at a steady state and during regeneration following hematopoietic stem cell transplantation (HST). RNA sequencing of lineage(-) bone marrow cells from C57/Bl6 mice revealed a broad transcriptional similarity between the sexes. However, we identified distinct sex differences in key biological pathways, with female cells showing reduced expression of signatures involved in inflammation and enrichment of genes related to glycolysis, hypoxia, and cell cycle regulation, suggesting a more quiescent and less inflammatory profile compared with male cells. To determine the functional impacts of the observed transcriptomic differences, we performed sex-matched and mismatched transplantation studies of lineage(-) donor cells. During short-term 56-day HST recovery, we found a male donor cell proliferative advantage, coinciding with elevated serum TNF-α, and a male recipient engraftment advantage, coinciding with increased serum CXCL12. Together, we show that sex-specific cell responses, marked by differing expression of pathways regulating metabolism, hypoxia, and inflammation, shape normal and regenerative hematopoiesis, with implications for the clinical understanding of hematopoietic function.
Competing Interests: Conflict of Interest Disclosure The authors have no conflicts of interest to declare.
(Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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