
Stem Cell Shape Regulates a Chondrogenic Versus Myogenic Fate Through Rac1 and N‐Cadherin
Author(s) -
Gao Lin,
McBeath Rowena,
Chen Christopher S.
Publication year - 2010
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.308
Subject(s) - chondrogenesis , microbiology and biotechnology , biology , cadherin , mesenchymal stem cell , cellular differentiation , rhoa , rac1 , stem cell , cell , signal transduction , biochemistry , gene
Human mesenchymal stem cells (hMSCs) are multipotent cells that can differentiate into many cell types. Chondrogenesis is induced in hMSCs cultured as a micromass pellet to mimic cellular condensation during cartilage development, and exposed to transforming growth factor β (TGFβ). Interestingly, TGFβ can also induce hMSC differentiation to smooth‐muscle‐like cell types, but it remains unclear what directs commitment between these two lineages. Our previous work revealed that cell shape regulates hMSC commitment between osteoblasts and adipocytes through RhoA signaling. Here we show that cell shape also confers a switch between chondrogenic and smooth muscle cell (SMC) fates. Adherent and well‐spread hMSCs stimulated with TGFβ3 upregulated SMC genes, whereas cells allowed to attach onto micropatterned substrates, but prevented from spreading and flattening, upregulated chondrogenic genes. Interestingly, cells undergoing SMC differentiation exhibited little change in RhoA, but significantly higher Rac1 activity than chondrogenic cells. Rac1 activation inhibited chondrogenesis and was necessary and sufficient for inducing SMC differentiation. Furthermore, TGFβ3 and Rac1 signaling upregulated N‐cadherin, which was required for SMC differentiation. These results demonstrate a chondrogenic‐SMC fate decision mediated by cell shape, Rac1, and N‐cadherin, and highlight the tight coupling between lineage commitment and the many changes in cell shape, cell‐matrix adhesion, and cell‐cell adhesion that occur during morphogenesis. S TEM C ELLS 2010;28:564–572