Inflammatorysignaling has been shown to be essential for stress hematopoiesis in adult bone marrow, either through increasing proliferation or by directing differentiation of hematopoieticstem and progenitorcells (HSPCs) toward myeloid or lymphoid lineages. However, its role in embryonic normal hematopoiesis has been unknown. Here, we demonstrate that in both zebrafish and mouse embryos, inflammatorysignaling is necessary and sufficient for HSPC emergence, in the absence of infection or pathological inflammation. Mechanistically, inflammatorysignalingregulateshemogenic endothelium-derived HSPC development through a conserved Toll-like receptor 4 (TLR4)-nuclear factor κ-light-chain enhancer of activated B core (NF-κB) signaling, which then promotes Notch activity, a well-known signal required for HSPC specification in vertebrates. Our findings establish a previously unrecognized link between inflammatorysignaling and HSPC emergence, and provide new insights into regenerative medicine and novel therapies to treat innate immune-related diseases.

He QP, Zhang CX, Wang L, Zhang PP, Ma DY, Lv JH, Liu F*. (2015) Inflammatory signaling regulates hematopoietic stem and progenitor cell emergence in vertebrates. Blood, 125(7):1098-1106.