Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells
Pro-fibrotic microenvironments of scars and tumors characterized by increased stiffness stimulate mesenchymal stromal cells (MSCs) to express α-smooth muscle actin (α-SMA). We investigated whether incorporation of α-SMA into contractile stress fibers regulates human MSC fate. Sorted α-SMA-positive M...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-06-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115001332 |
| _version_ | 1819132041758769152 |
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| author | Nilesh P. Talele Julie Fradette John E. Davies Andras Kapus Boris Hinz |
| author_facet | Nilesh P. Talele Julie Fradette John E. Davies Andras Kapus Boris Hinz |
| author_sort | Nilesh P. Talele |
| collection | DOAJ |
| description | Pro-fibrotic microenvironments of scars and tumors characterized by increased stiffness stimulate mesenchymal stromal cells (MSCs) to express α-smooth muscle actin (α-SMA). We investigated whether incorporation of α-SMA into contractile stress fibers regulates human MSC fate. Sorted α-SMA-positive MSCs exhibited high contractile activity, low clonogenicity, and differentiation potential limited to osteogenesis. Knockdown of α-SMA was sufficient to restore clonogenicity and adipogenesis in MSCs. Conversely, α-SMA overexpression induced YAP translocation to the nucleus and reduced the high clonogenicity and adipogenic potential of α-SMA-negative MSCs. Inhibition of YAP rescued the decreased adipogenic differentiation potential induced by α-SMA, establishing a mechanistic link between matrix stiffness, α-SMA, YAP, and MSC differentiation. Consistent with in vitro findings, nuclear localization of YAP was positively correlated in α-SMA expressing stromal cells of adiposarcoma and osteosarcoma. We propose that α-SMA mediated contraction plays a critical role in mechanically regulating MSC fate by controlling YAP/TAZ activation. |
| first_indexed | 2024-12-22T09:25:06Z |
| format | Article |
| id | doaj.art-ff4057567d6f4a0bb09d62ef5c5caf6b |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-22T09:25:06Z |
| publishDate | 2015-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-ff4057567d6f4a0bb09d62ef5c5caf6b2022-12-21T18:31:07ZengElsevierStem Cell Reports2213-67112015-06-01461016103010.1016/j.stemcr.2015.05.004Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal CellsNilesh P. Talele0Julie Fradette1John E. Davies2Andras Kapus3Boris Hinz4Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, CanadaDivision of Regenerative Medicine, Department of Surgery, Centre de recherche en organogénèse expérimentale de l’Université Laval / LOEX, CHU de Québec Research Centre, Faculty of Medicine, Université Laval, Québec, QC G1J 1Z4, CanadaInstitute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, CanadaKeenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, and Department of Surgery, University of Toronto, Toronto, ON M5B 1W8, CanadaLaboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, CanadaPro-fibrotic microenvironments of scars and tumors characterized by increased stiffness stimulate mesenchymal stromal cells (MSCs) to express α-smooth muscle actin (α-SMA). We investigated whether incorporation of α-SMA into contractile stress fibers regulates human MSC fate. Sorted α-SMA-positive MSCs exhibited high contractile activity, low clonogenicity, and differentiation potential limited to osteogenesis. Knockdown of α-SMA was sufficient to restore clonogenicity and adipogenesis in MSCs. Conversely, α-SMA overexpression induced YAP translocation to the nucleus and reduced the high clonogenicity and adipogenic potential of α-SMA-negative MSCs. Inhibition of YAP rescued the decreased adipogenic differentiation potential induced by α-SMA, establishing a mechanistic link between matrix stiffness, α-SMA, YAP, and MSC differentiation. Consistent with in vitro findings, nuclear localization of YAP was positively correlated in α-SMA expressing stromal cells of adiposarcoma and osteosarcoma. We propose that α-SMA mediated contraction plays a critical role in mechanically regulating MSC fate by controlling YAP/TAZ activation.http://www.sciencedirect.com/science/article/pii/S2213671115001332 |
| spellingShingle | Nilesh P. Talele Julie Fradette John E. Davies Andras Kapus Boris Hinz Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells Stem Cell Reports |
| title | Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells |
| title_full | Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells |
| title_fullStr | Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells |
| title_full_unstemmed | Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells |
| title_short | Expression of α-Smooth Muscle Actin Determines the Fate of Mesenchymal Stromal Cells |
| title_sort | expression of α smooth muscle actin determines the fate of mesenchymal stromal cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115001332 |
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