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Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells.
Smith, Quinton; Macklin, Bria; Chan, Xin Yi; Jones, Hannah; Trempel, Michelle; Yoder, Mervin C; Gerecht, Sharon.
Afiliação
  • Smith Q; Department of Chemical and Biomolecular Engineering, Physical Sciences-Oncology Center and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Macklin B; Department of Chemical and Biomolecular Engineering, Physical Sciences-Oncology Center and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Chan XY; Department of Chemical and Biomolecular Engineering, Physical Sciences-Oncology Center and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Jones H; Department of Chemical and Biomolecular Engineering, Physical Sciences-Oncology Center and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Trempel M; Department of Chemical and Biomolecular Engineering, Physical Sciences-Oncology Center and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Yoder MC; Department of Pediatrics, Biochemistry, and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Gerecht S; Department of Chemical and Biomolecular Engineering, Physical Sciences-Oncology Center and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address:
Cell Rep ; 24(4): 895-908.e6, 2018 07 24.
Article em En | MEDLINE | ID: mdl-30044986
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cílios / Células-Tronco Pluripotentes / Células Endoteliais / Desacetilase 6 de Histona Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cílios / Células-Tronco Pluripotentes / Células Endoteliais / Desacetilase 6 de Histona Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos