Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells | Zendy

Quinton Smith | Zendy; Bria Macklin | Zendy; Xin Yi Chan | Zendy; Hannah E. Jones | Zendy; Michelle Trempel | Zendy; Mervin C. Yöder | Zendy; Sharon Gerecht | Zendy

Open Access

Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells

Author(s) -

Quinton Smith,

Bria Macklin,

Xin Yi Chan,

Hannah E. Jones,

Michelle Trempel,

Mervin C. Yöder,

Sharon Gerecht

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.06.083

Subject(s) - ciliogenesis , cilium , microbiology and biotechnology , mechanosensation , induced pluripotent stem cell , hdac6 , biology , intraflagellar transport , stem cell , chemistry , histone deacetylase , genetics , histone , gene , embryonic stem cell , receptor , flagellum , ion channel

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 stress in vitro in 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 closure in 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.

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