Ciclopirox ethanolamine preserves the immature state of human HSCs by mediating intracellular iron content.

ABSTRACT: Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. To elucidate regulatory mechanisms governing the maintenance and propagation of human HSCs ex vivo, we screened libraries of annotated small molecules in human cord blood cells using an optimized assay for detection of functional HSCs during culture. We found that the antifungal agent ciclopirox ethanolamine (CPX) selectively supported immature CD34+CD90+ cells during culture and enhanced their long-term in vivo repopulation capacity. Purified HSCs treated with CPX showed a reduced cell division rate and an enrichment of HSC-specific gene expression patterns. Mechanistically, we found that the HSC stimulating effect of CPX was directly mediated by chelation of the intra

SUBMITTER: Talkhoncheh MS 

PROVIDER: S-EPMC10758717 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature