Uncovering the emergence of HSCs in the human fetal bone marrow by single-cell RNA-seq analysis

During fetal development, human hematopoietic stem cells (HSCs) colonize the bone marrow (BM), where they self-renew and sustain hematopoiesis throughout life; however, the precise timepoint at which HSCs seed the BM is unclear. We used single-cell RNA-sequencing to map the transcriptomic landscape of human fetal BM and spleen hematopoietic stem/progenitor cells (HSPCs) and their microenvironment from 10 to 14 post-conception weeks (PCWs). We further demonstrated that functional HSCs capable of reconstituting long-term multi-lineage hematopoiesis in adult NOG mice do not emerge in the BM until 12 PCWs. In contrast, functional HSCs were not detected in the spleen by 14 PCWs. By comparing the niche-HSPC interactions between BM and spleen, we identified ligand-receptor pairs likely to be involved in fetal HSC migration and maintenance. Our work paves the way for research into the mechanisms underlying HSC colonization in human fetal BM and provides invaluable resources for future studies on HSC development. [Display omitted] •A single-cell transcriptomic landscape of human fetal BM and spleen is constructed•Functional HSCs are present in human fetal BM at 12 PCWs, but not in spleen•Potential ligand-receptor pairs acting as niche factors for fetal HSCs are identified Zheng et al. provide a transcriptomic landscape of hematopoietic stem and progenitor cells and microenvironment in human fetal bone marrow and spleen. They uncover the precise timepoint at which hematopoietic stem cells (HSCs) seed fetal bone marrow and key niche cells and ligand-receptor interactions involved in the human HSC colonization.