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

doi:10.1021/nn4058984

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 journal › Article › peer-review

82 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 language	English
Pages (from-to)	2033-2047
Number of pages	15
Journal	ACS Nano
Volume	8
Issue number	3
DOIs	https://doi.org/10.1021/nn4058984
Publication status	Published - 2014 Mar 25
Externally published	Yes

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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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

Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure. / Mosqueira, Diogo; Pagliari, Stefania; Uto, Koichiro; Ebara, Mitsuhiro; Romanazzo, Sara; Escobedo-Lucea, Carmen; Nakanishi, Jun; Taniguchi, Akiyoshi; Franzese, Ornella; Di Nardo, Paolo; Goumans, Marie José; Traversa, Enrico; Pinto-Do-Ó, Perpetua; Aoyagi, Takao; Forte, Giancarlo.

In: ACS Nano, Vol. 8, No. 3, 25.03.2014, p. 2033-2047.

Research output: Contribution to journal › Article › peer-review

Mosqueira, D, Pagliari, S, Uto, K, Ebara, M, Romanazzo, S, Escobedo-Lucea, C, Nakanishi, J, Taniguchi, A, Franzese, O, Di Nardo, P, Goumans, MJ, 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, vol. 8, no. 3, pp. 2033-2047. https://doi.org/10.1021/nn4058984

Mosqueira, Diogo ; Pagliari, Stefania ; Uto, Koichiro ; Ebara, Mitsuhiro ; Romanazzo, Sara ; Escobedo-Lucea, Carmen ; Nakanishi, Jun ; Taniguchi, Akiyoshi ; Franzese, Ornella ; Di Nardo, Paolo ; Goumans, Marie José ; Traversa, Enrico ; Pinto-Do-Ó, Perpetua ; Aoyagi, Takao ; Forte, Giancarlo. / Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure. In: ACS Nano. 2014 ; Vol. 8, No. 3. pp. 2033-2047.

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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.",

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AU - Romanazzo, Sara

AU - Escobedo-Lucea, Carmen

AU - Nakanishi, Jun

AU - Taniguchi, Akiyoshi

AU - Franzese, Ornella

AU - Di Nardo, Paolo

AU - Goumans, Marie José

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AU - Pinto-Do-Ó, Perpetua

AU - Aoyagi, Takao

AU - Forte, Giancarlo

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

Abstract

Keywords

ASJC Scopus subject areas

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