Making Blood from the Vessel: Extrinsic and Environmental Cues Guiding the Endothelial-to-Hematopoietic Transition

It is increasingly recognized that specialized subsets of endothelial cells carry out unique functions in specific organs and regions of the vascular tree. Perhaps the most striking example of this specialization is the ability to contribute to the generation of the blood system, in which a distinct population of “hemogenic” endothelial cells in the embryo transforms irreversibly into hematopoietic stem and progenitor cells that produce circulating erythroid, myeloid and lymphoid cells for the lifetime of an animal. This review will focus on recent advances made in the zebrafish model organism uncovering the extrinsic and environmental factors that facilitate hemogenic commitment and the process of endothelial-to-hematopoietic transition that produces blood stem cells. We highlight in particular biomechanical influences of hemodynamic forces and the extracellular matrix, metabolic and sterile inflammatory cues present during this developmental stage, and outline new avenues opened by transcriptomic-based approaches to decipher cell–cell communication mechanisms as examples of key signals in the embryonic niche that regulate hematopoiesis.