Differentiation latency, cell division symmetry, and dormancy signatures define fetal liver HSCs at single cell resolution.

ABSTRACT: Decoding the gene regulatory mechanisms and signaling interactions that orchestrate the self-renewal of hematopoietic stem cells (HSCs) during their expansion in the fetal liver (FL) could unlock novel therapeutic strategies to expand transplantable HSCs, a long-standing challenge. Here, to explore intrinsic and extrinsic regulation of FL-HSC self-renewal at the single cell level, we engineered a culture platform designed to recapitulate the FL endothelial niche, which supports the ex vivo amplification of serially engraftable HSCs. Leveraging this platform in combination with single cell index flow cytometry, live imaging, serial transplantation assays, and single cell RNA-sequencing, we uncovered previously unrecognized heterogeneity within immunophenotypically defined FL-HSCs. Specifica

SUBMITTER: Ishida T 

PROVIDER: S-EPMC10274697 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature