| Substrate stiffness affects early differentiation events in embryonic stem cells. | |
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MedLine Citation:
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PMID: 19768669 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Embryonic stem cells (ESC) are both a potential source of cells for tissue replacement therapies and an accessible tool to model early embryonic development. Chemical factors such as soluble growth factors and insoluble components of the extracellular matrix are known to affect the differentiation of murine ESCs. However, there is also evidence to suggest that undifferentiated cells can both sense the mechanical properties of their environment and differentiate accordingly. By growing ESCs on flexible polydimethylsiloxane substrates with varying stiffness, we tested the hypothesis that substrate stiffness can influence ESC differentiation. While cell attachment was unaffected by the stiffness of the growth substrate, cell spreading and cell growth were all increased as a function of substrate stiffness. Similarly, several genes expressed in the primitive streak during gastrulation and implicated in early mesendoderm differentiation, such as Brachyury, Mixl1 and Eomes, were upregulated in cell cultures on stiffer compared to softer substrates. Finally, we demonstrated that osteogenic differentiation of ESCs was enhanced on stiff substrates compared to soft substrates, illustrating that the mechanical environment can play a role in both early and terminal ESC differentiation. Our results suggest a fundamental role for mechanosensing in mammalian development and illustrate that the mechanical environment should be taken into consideration when engineering implantable scaffolds or when producing therapeutically relevant cell populations in vitro. |
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Authors:
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Nicholas D Evans; Caterina Minelli; Eileen Gentleman; Vanessa LaPointe; Sameer N Patankar; Maria Kallivretaki; Xinyong Chen; Clive J Roberts; Molly M Stevens |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-21 |
Journal Detail:
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Title: European cells & materials Volume: 18 ISSN: 1473-2262 ISO Abbreviation: Eur Cell Mater Publication Date: 2009 |
Date Detail:
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Created Date: 2009-09-21 Completed Date: 2010-01-14 Revised Date: 2012-06-05 |
Medline Journal Info:
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Nlm Unique ID: 100973416 Medline TA: Eur Cell Mater Country: Scotland |
Other Details:
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Languages: eng Pagination: 1-13; discussion 13-4 Citation Subset: IM |
Affiliation:
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Department of Materials, Imperial College London, London, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Adhesion / drug effects Cell Differentiation / drug effects* Cell Movement / drug effects Cell Proliferation / drug effects Cells, Cultured Dimethylpolysiloxanes / chemistry, pharmacology* Elasticity Embryonic Stem Cells / cytology, drug effects*, metabolism Female Fetal Proteins / genetics Fibroblast Growth Factor 5 / genetics Focal Adhesion Kinase 1 / metabolism GATA6 Transcription Factor / genetics Gene Expression / drug effects Hepatocyte Nuclear Factor 3-beta / genetics Homeodomain Proteins / genetics Mice Reverse Transcriptase Polymerase Chain Reaction SOXB1 Transcription Factors / genetics T-Box Domain Proteins / genetics Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Brachyury protein; 0/Dimethylpolysiloxanes; 0/Fetal Proteins; 0/Fgf5 protein, mouse; 0/Foxa2 protein, mouse; 0/GATA6 Transcription Factor; 0/Gata6 protein, mouse; 0/Homeodomain Proteins; 0/Nanog protein, mouse; 0/SOXB1 Transcription Factors; 0/Sox1 protein, mouse; 0/T-Box Domain Proteins; 129653-64-1/Fibroblast Growth Factor 5; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; 63148-62-9/baysilon; EC 2.7.10.1/Focal Adhesion Kinase 1; EC 2.7.10.2/Ptk2 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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