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Resolution of Inflammation Increases hematopoietic Stem Cell Number and Erythropoiesis

ABSTRACT: Hematopoietic stem cells (HSC) are essential for blood production throughout our lives. To find new factors that control HSC formation, we screened for bioactive lipid mediators derived from n-3 polyunsaturated fatty acid (n-3 PUFA). n-3 PUFA-derived lipid mediators include compounds called specialized pro-resolving mediators (SPMs), which help resolve inflammation and fight infection. In this study, we investigated the pro-hematopoietic effects of n-3 PUFA-derived SPMs. We exposed zebrafish embryos to various SPMs and found one SPM compound derived from n-3 docosapentaenoic acid, 7(S),17(s)-dihydroxy docosapentaenoic acid (7,17-diHDPAn-3) that increases the expression of HSC markers like cmyb, scl/tal-1, and runx1. 7,17-diHDPAn-3 exposure also increases the expression of gata1, an erythroid progenitor marker, leading to a significant rise in erythrocyte numbers. We confirmed these effects on both primitive and definitive erythropoiesis in zebrafish. Importantly, the production of platelets, that share a common progenitor with erythrocytes, was unaffected. Further metabolomic and RNA-sequencing analysis revealed that 7,17-diHDPAn-3 exposure slightly altered the metabolic profile of RBCs and regulated the expression of the xpo1b and hsp90 genes involved in RBC maturation and heme synthesis, respectively. To understand the link between inflammation resolution and HSC formation, we exposed zebrafish to dexamethasone, which increases the expression of the HSC markers cmyb, and runx1. Co-treatment with 7,17-diHDPAn-3 and dexamethasone had a synergistic effect, demonstrating a novel role for inflammation resolution in stem cell formation. Our work identifies 7,17-diHDPAn-3 as a suitable natural compound to increase HSC number and erythropoiesis in vivo and might be considered for subsequent clinical analysis.

ORGANISM(S): Danio rerio

PROVIDER: GSE282805 | GEO | 2026/07/08

REPOSITORIES: GEO

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Resolution of Inflammation Increases hematopoietic Stem Cell Number and Erythropoiesis

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