Open AccessIn situ mechanotransduction via vinculin regulates stem cell differentiation
Author(s) -
Holle Andrew W.,
Tang Xinyi,
Vijayraghavan Deepthi,
Vincent Ludovic G.,
Fuhrmann Alexander,
Choi Yu Suk,
Álamo Juan C.,
Engler Adam J.
Publication year - 2013
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1490
Subject(s) - vinculin , mechanotransduction , microbiology and biotechnology , runx2 , myod , gene knockdown , biology , focal adhesion , transcription factor , cell adhesion , cellular differentiation , extracellular matrix , stem cell , signal transduction , myogenesis , myocyte , cell , cell culture , genetics , gene
A bstract Human mesenchymal stem cell (hMSC) proliferation, migration, and differentiation have all been linked to extracellular matrix stiffness, yet the signaling pathway(s) that are necessary for mechanotransduction remain unproven. Vinculin has been implicated as a mechanosensor in vitro, but here we demonstrate its ability to also regulate stem cell behavior, including hMSC differentiation. RNA interference‐mediated vinculin knockdown significantly decreased stiffness‐induced MyoD, a muscle transcription factor, but not Runx2, an osteoblast transcription factor, and impaired stiffness‐mediated migration. A kinase binding accessibility screen predicted a cryptic MAPK1 signaling site in vinculin which could regulate these behaviors. Indeed, reintroduction of vinculin domains into knocked down cells indicated that MAPK1 binding site‐containing vinculin constructs were necessary for hMSC expression of MyoD. Vinculin knockdown does not appear to interfere with focal adhesion assembly, significantly alter adhesive properties, or diminish cell traction force generation, indicating that its knockdown only adversely affected MAPK1 signaling. These data provide some of the first evidence that a force‐sensitive adhesion protein can regulate stem cell fate. S tem C ells 2013;31:2467–2477