Substrate stiffness affects early differentiation events in embryonic stem cells.
Détails
ID Serval
serval:BIB_00120C9FEBF4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Substrate stiffness affects early differentiation events in embryonic stem cells.
Périodique
European cells & materials
ISSN
1473-2262 (Electronic)
ISSN-L
1473-2262
Statut éditorial
Publié
Date de publication
21/09/2009
Peer-reviewed
Oui
Volume
18
Pages
1-13; discussion 13-4
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
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.
Mots-clé
Animals, Blotting, Western, Cell Adhesion/drug effects, Cell Differentiation/drug effects, Cell Movement/drug effects, Cell Proliferation/drug effects, Cells, Cultured, Dimethylpolysiloxanes/chemistry, Dimethylpolysiloxanes/pharmacology, Elasticity, Embryonic Stem Cells/cytology, Embryonic Stem Cells/drug effects, Embryonic Stem Cells/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, Nanog Homeobox Protein, Reverse Transcriptase Polymerase Chain Reaction, SOXB1 Transcription Factors/genetics, T-Box Domain Proteins/genetics, Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/01/2024 10:14
Dernière modification de la notice
13/01/2024 7:10