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MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells
The use of biochemical signaling to derive smooth muscle cells (SMCs) from mesenchymal stem cells (MSCs) has been explored, but the induction of a fully functional SMC phenotype remains to be a major challenge. Cell morphology has been shown to regulate MSC differentiation into various lineages, inc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825513/ https://www.ncbi.nlm.nih.gov/pubmed/30884320 http://dx.doi.org/10.1016/j.biomaterials.2019.03.003 |
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author | Yeh, Yi-Ting Wei, Josh Thorossian, Satenick Nguyen, Katherine Hoffman, Clarissa del Álamo, Juan C. Serrano, Ricardo Li, Yi-Shuan Julie Wang, Kuei-Chun Chien, Shu |
author_facet | Yeh, Yi-Ting Wei, Josh Thorossian, Satenick Nguyen, Katherine Hoffman, Clarissa del Álamo, Juan C. Serrano, Ricardo Li, Yi-Shuan Julie Wang, Kuei-Chun Chien, Shu |
author_sort | Yeh, Yi-Ting |
collection | PubMed |
description | The use of biochemical signaling to derive smooth muscle cells (SMCs) from mesenchymal stem cells (MSCs) has been explored, but the induction of a fully functional SMC phenotype remains to be a major challenge. Cell morphology has been shown to regulate MSC differentiation into various lineages, including SMCs. We engineered substrates with microgrooves to induce cell elongation to study the mechanism underlying the MSC shape modulation in SMC differentiation. In comparison to those on flat substrates, MSCs cultured on engineered substrates were elongated with increased aspect ratios for both cell body and nucleus, as well as augmented cytoskeletal tensions. Biochemical studies indicated that the microgroove-elongated cells expressed significantly higher levels of SMC markers. MicroRNA analyses showed that up-regulation of miR-145 and the consequent repression of KLF4 in these elongated cells promoted MSC-to-SMC differentiation. Rho/ROCK inhibitions, which impair cytoskeletal tension, attenuated cell and nuclear elongations and disrupted the miR-145/KLF4 regulation for SMC differentiation. Furthermore, cell traction force measurements showed that miR-145 is essential for the functional contractility in the microgroove-induced SMC differentiation. Collectively, our findings demonstrate that, through a Rho-ROCK/miR-145/KLF4 pathway, the elongated cell shape serves as a decisive geometric cue to direct MSC differentiation into functional SMCs. |
format | Online Article Text |
id | pubmed-6825513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68255132020-06-01 MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells Yeh, Yi-Ting Wei, Josh Thorossian, Satenick Nguyen, Katherine Hoffman, Clarissa del Álamo, Juan C. Serrano, Ricardo Li, Yi-Shuan Julie Wang, Kuei-Chun Chien, Shu Biomaterials Article The use of biochemical signaling to derive smooth muscle cells (SMCs) from mesenchymal stem cells (MSCs) has been explored, but the induction of a fully functional SMC phenotype remains to be a major challenge. Cell morphology has been shown to regulate MSC differentiation into various lineages, including SMCs. We engineered substrates with microgrooves to induce cell elongation to study the mechanism underlying the MSC shape modulation in SMC differentiation. In comparison to those on flat substrates, MSCs cultured on engineered substrates were elongated with increased aspect ratios for both cell body and nucleus, as well as augmented cytoskeletal tensions. Biochemical studies indicated that the microgroove-elongated cells expressed significantly higher levels of SMC markers. MicroRNA analyses showed that up-regulation of miR-145 and the consequent repression of KLF4 in these elongated cells promoted MSC-to-SMC differentiation. Rho/ROCK inhibitions, which impair cytoskeletal tension, attenuated cell and nuclear elongations and disrupted the miR-145/KLF4 regulation for SMC differentiation. Furthermore, cell traction force measurements showed that miR-145 is essential for the functional contractility in the microgroove-induced SMC differentiation. Collectively, our findings demonstrate that, through a Rho-ROCK/miR-145/KLF4 pathway, the elongated cell shape serves as a decisive geometric cue to direct MSC differentiation into functional SMCs. 2019-03-08 2019-06 /pmc/articles/PMC6825513/ /pubmed/30884320 http://dx.doi.org/10.1016/j.biomaterials.2019.03.003 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Yeh, Yi-Ting Wei, Josh Thorossian, Satenick Nguyen, Katherine Hoffman, Clarissa del Álamo, Juan C. Serrano, Ricardo Li, Yi-Shuan Julie Wang, Kuei-Chun Chien, Shu MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells |
title | MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells |
title_full | MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells |
title_fullStr | MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells |
title_full_unstemmed | MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells |
title_short | MiR-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells |
title_sort | mir-145 mediates cell morphology-regulated mesenchymal stem cell differentiation to smooth muscle cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825513/ https://www.ncbi.nlm.nih.gov/pubmed/30884320 http://dx.doi.org/10.1016/j.biomaterials.2019.03.003 |
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