In vertebrates, hematopoietic stem cells (HSCs) arise from the hemogenic endothelium in the dorsal aorta during a brief developmental window. In Cell, Traver and colleagues show that signaling by tumor-necrosis factor (TNF) through its receptor TNFR2 is required for the emergence of HSCs from the aortic endothelium in zebrafish embryos, but signaling via its receptor TNFR1 is not. TNF signaling induces expression of the Notch ligand Jagged1 to activate Notch1 in the hemogenic endothelium and also activates the transcription factor NF-κB. Both Notch1 and NF-κB are required for HSC specification. These effects are independent of the role of TNF in the developing vasculature or the induction of apoptosis in endothelial cells. Yolk sack–derived primitive neutrophils are the main source of TNF for the induction of HSCs, which indicates a role for these transient immune cells in definitive hematopoiesis.

Cell 159, 1070–1085 (2014)