Sclerotomal hematopoiesis in vertebrate embryos contributes to robustness of the blood system

During vertebrate embryogenesis, hematopoietic stem cells (HSCs) are believed to almost exclusively arise from hemogenic endothelial cells (ECs) of the dorsal aorta through endothelial-to-hematopoietic transition (EHT). It remains elusive whether HSCs can be generated by other tissues. Sclerotomal cells (SCs) in embryonic somites majorly form vertebrae and ribs, and some SCs may also insert into aortic endothelia. Here we show that a subset of SCs directly enter the vascular lumen to become hematopoietic stem and progenitor cells (HSPCs) in an EHT-independent way in both zebrafish and mouse embryos. The sclerotome-derived HSPCs (scHSPCs) contribute to various blood cells throughout lifetime. The proportion of scHSPCs increased dramatically when endothelium hematopoiesis is defective. Thus, the sclerotomal hematopoiesis is evolutionarily conserved and would ensure the robustness of hematopoiesis.