Model depicting the role of β3-integrin in TPO-dependent regulation of HSC division leading to the maintenance of LTR ability. Integrin-β3 bidirectional signaling and TPO were dependent on each other in the maintenance of HSCs. (A) TPO/c-mpl signaling leads to conformational change of integrin-αvβ3 into high-affinity form for their ligands (the activation of integrin-αvβ3) by inducing inside-out signaling. (B) Outside-in signaling via Tyr747 phosphorylation of integrin-β3 induces enhanced expression of stemness-related genes after their ligation.