Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure

Diogo Mosqueira, Stefania Pagliari, Koichiro Uto, Mitsuhiro Ebara, Sara Romanazzo, Carmen Escobedo-Lucea, Jun Nakanishi, Akiyoshi Taniguchi, Ornella Franzese, Paolo Di Nardo, Marie José Goumans, Enrico Traversa, Perpetua Pinto-Do-Ó, Takao Aoyagi, Giancarlo Forte

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design.

Original languageEnglish
Pages (from-to)2033-2047
Number of pages15
JournalACS Nano
Volume8
Issue number3
DOIs
Publication statusPublished - 2014 Mar 25

Keywords

  • YAP/TAZ
  • adult cardiac progenitor cell
  • cardiac differentiation
  • mechano- transduction
  • substrate nanotopography

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Mosqueira, D., Pagliari, S., Uto, K., Ebara, M., Romanazzo, S., Escobedo-Lucea, C., Nakanishi, J., Taniguchi, A., Franzese, O., Di Nardo, P., Goumans, M. J., Traversa, E., Pinto-Do-Ó, P., Aoyagi, T., & Forte, G. (2014). Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure. ACS Nano, 8(3), 2033-2047. https://doi.org/10.1021/nn4058984