Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells.
Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells.
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差异 HDAC6 活性调节纤毛发生和随后源自多能干细胞的内皮细胞的机械传感。
DOI：
10.1016/j.celrep.2018.06.083
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发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Gerecht,Sharon
中科院分区：
文献类型：
--
作者：
Smith,Quinton;Macklin,Bria;Chan,XinYi;Jones,Hannah;Trempel,Michelle;Yoder,MervinC;Gerecht,Sharon
初级纤毛在机械感觉中的作用在内皮细胞（EC）剪切反应中是必不可少的。在这里，我们发现，静脉，毛细血管和祖细胞EC响应剪切应力体外纤毛依赖的方式。然后，我们证明了在人诱导多能干细胞（hiPSC）衍生的EC中的初级纤毛组装在不同的细胞系之间变化，分化方案的影响很小。缺乏纤毛hiPSC衍生的EC不与剪切应力对齐，缺乏应力纤维组装，在体外伤口闭合期间具有不协调的迁移，并且在剪切暴露时具有异常的钙内流。转录分析揭示了不同hiPSC衍生的EC中参与纤毛发生的调控基因的变化。此外，在缺乏纤毛的hiPSC-EC中抑制组蛋白脱乙酰基酶6（HDAC 6）活性拯救纤毛形成并恢复机械感测。总之，这些结果显示了初级纤毛在hiPSC-EC机械响应性中的重要性，并且其通过HDAC 6活性的调节在hiPSC-EC中不同。
The role of primary cilia in mechanosensation is essential in endothelial cell (EC) shear responsiveness. Here, we find that venous, capillary, and progenitor ECs respond to shear stressin vitroin a cilia-dependent manner. We then demonstrate that primary cilia assembly in human induced pluripotent stem cell (hiPSC)-derived ECs varies between different cell lines with marginal influence of differentiation protocol. hiPSC-derived ECs lacking cilia do not align to shear stress, lack stress fiber assembly, have uncoordinated migration during wound closurein vitro, and have aberrant calcium influx upon shear exposure. Transcriptional analysis reveals variation in regulatory genes involved in ciliogenesis among different hiPSC-derived ECs. Moreover, inhibition of histone deacetylase 6 (HDAC6) activity in hiPSC-ECs lacking cilia rescues cilia formation and restores mechanical sensing. Taken together, these results show the importance of primary cilia in hiPSC-EC mechano-responsiveness and its modulation through HDAC6 activity varies among hiPSC-ECs.