Centrosome reduction and redistribution of pericentriolar material (PCM) coincides with cardiomyocyte transitions to a post-mitotic and matured state. However, it is unclear whether centrosome changes are a cause or consequence of terminal differentiation. We validated that centrosomes were intact and functional in proliferative human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), consistent with their immature phenotype. We generated acentrosomal hPSC-CMs, through pharmacological inhibition of centriole duplication, and showed that centrosome loss was sufficient to promote post-mitotic transitions and aspects of cardiomyocyte maturation. As Hippo kinases are activated during post-natal cardiac maturation, we pharmacologically activated the Hippo pathway using C19, which was sufficient to trigger centrosome disassembly and relocalization of PCM components to perinuclear membranes. This was due to specific activation of Hippo kinases, as direct inhibition of YAP-TEAD interactions with verteporfin had no effect on centrosome organization. This suggests that Hippo kinase-centrosome remodeling may play a direct role in cardiac maturation.

中心体减少和重分布周围膜材料（PCM）与心肌细胞过渡到有丝分裂后和成熟状态相吻合。然而，不清楚中心体变化是终末分化的原因还是结果。我们验证了中心体在人类多能干细胞源性心肌细胞（hPSC-CMs）的增殖中是完整的，并且与其未成熟的表型一致。我们通过药理学抑制中心粒重复生成了人体hPSC-CMs，并显示中心体损失足以促进有丝分裂后过渡和心肌细胞成熟的各个方面。由于Hippo激酶在出生后心脏成熟过程中被激活，因此我们使用C19在药理上激活了Hippo途径，这足以触发中心体拆卸和PCM组件重新定位到核周膜。这是由于Hippo激酶的特异性激活所致，因为直接抑制YAP-TEAD与韦替泊芬的相互作用对中心体组织没有影响。这表明，河马激酶中心体重塑可能在心脏成熟中起直接作用。