Biased PAR1 signaling regulates HSC quiescence and mobility. PAR1 activation by EPCR-aPC promotes inhibition of endothelial NO synthase (eNOS), low NO and ROS levels, and suppression of Cdc42 activity and increased VLA (integrin α4)–mediated adhesion to niche ligands. Biased thrombin-PAR1 signaling releases EPCR by TACE shedding and upregulates NO, Cdc42 activity, and motility.