YAP REGULATES HEMATOPOIETIC STEM CELL FORMATION IN RESPONSE TO THE BIOMECHANICAL FORCES OF BLOOD FLOW

Abstract

Hematopoietic stem cells (HSCs) are born from cells in the dorsal aorta that adopt hematopoietic potential and commitment during development. Physical forces, namely wall shear stress (WSS) and cyclic stretch (CS), produced by hemodynamic blood flow are required to generate HSCs from arterial endothelium, but the mechanisms by which these forces are transduced into a “stemness” regulatory program remain unknown. Using a novel “dorsal-aorta-on-a-chip” microfluidic platform, we demonstrate that exposure to WSS and CS increases expression of the hematopoietic transcription factor RUNX1 in human CD34+ hemogenic endothelial cells derived from induced pluripotent stem cells. Notably, CS specifical..