Tissue-Specific Stem Cells

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Stem Cell Shape Regulates a Chondrogenic Versus Myogenic Fate Through Rac1 and N-Cadherin†

  1. Lin Gao1,
  2. Rowena McBeath2,
  3. Christopher S. Chen1,‡,*

Article first published online: 15 JAN 2010

DOI: 10.1002/stem.308

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 3, pages 564–572, March 2010

Additional Information

How to Cite

Gao, L., McBeath, R. and Chen, C. S. (2010), Stem Cell Shape Regulates a Chondrogenic Versus Myogenic Fate Through Rac1 and N-Cadherin. STEM CELLS, 28: 564–572. doi: 10.1002/stem.308

Author Information

  1. 1

    Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA

  2. 2

    Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

  1. ‡

    Telephone: 215-746-1754; Fax: 215-746-1752

*Department of Bioengineering, University of Pennsylvania, 510 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104

  1. †

    Author contributions: L.G.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; R.M.: conception and design, collection and assembly of data, data analysis and interpretation; C.S.C.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.

  2. Disclosure of potential conflicts of interest is found at the end of this article.

  3. First published online in STEM CELLSEXPRESS January 15, 2010.

  4. ‡

    Telephone: 215-746-1754; Fax: 215-746-1752

Publication History

  1. Issue published online: 24 MAR 2010
  2. Article first published online: 15 JAN 2010
  3. Accepted manuscript online: 15 JAN 2010 12:00AM EST
  4. Manuscript Accepted: 7 JAN 2010
  5. Manuscript Received: 19 MAY 2009

Funded by

  • NIH. Grant Numbers: EB00262, HL73305, GM74048
  • University of Pennsylvania Institute for Regenerative Medicine, and Center for Musculoskeletal Disorders
  • NIH Medical Scientist Training Program

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Keywords:

  • Mesenchymal stem cells;
  • Cell shape;
  • Chondrogenesis;
  • Smooth muscle cells;
  • Rac1;
  • N-cadherin

Abstract

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. STEM CELLS 2010;28:564–572

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