Figure 2.

Mechanical cues in the aortic microenvironment impacting HSC production via EHT. (A) With the onset of blood circulation in the dorsal aorta, Runx1-expressing hemogenic endothelial cells are subject to the perpendicular hemodynamic forces of wall shear stress and cyclic stretch. Additional cues are presented by the extracellular matrix, which must be remodeled to allow the extravasation of newly minted HSCs and the completion of EHT. Other mechanical stimuli may be mediated by the content of the plasma itself, i.e., blood viscosity and cellular composition, but this requires further investigation. (B) WSS and CS have unique intracellular effects in HE. WSS upregulates expression of the TF KLF2A, which promotes expression of nitric oxide synthases. WSS also stimulates production of prostaglandin E2 and calcium influx, both with pro-hematopoietic effects on EHT. CS directly induces nuclear localization of the YAP TF, stimulating expression of its canonical target genes via mechanotransduction. Other genes that might be regulated by these TFs to orchestrate EHT remain to be identified. CS cyclic stretch, EHT endothelial-to-hematopoietic-transition, HEC hemogenic endothelial cell, HSC hematopoietic stem cell, MMP matrix metalloproteinase, TF transcription factor, WSS wall shear stress. Figure created with BioRender.com.