Transforming Growth Factor-β and Notch Signaling Mediate Stem Cell Differentiation into Smooth Muscle Cells (original) (raw)
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Joint Graduate Program in Bioengineering, University of California Berkeley, Berkeley, California, and University of California San Francisco
, San Francisco, California,
USA
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Joint Graduate Program in Bioengineering, University of California Berkeley, Berkeley, California, and University of California San Francisco
, San Francisco, California,
USA
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Joint Graduate Program in Bioengineering, University of California Berkeley, Berkeley, California, and University of California San Francisco
, San Francisco, California,
USA
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Department of Bioengineering, University of California
, Berkeley, Berkeley, California,
USA
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Ahra Kim ,
Department of Bioengineering, University of California
, Berkeley, Berkeley, California,
USA
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Department of Bioengineering, University of California
, Berkeley, Berkeley, California,
USA
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Department of Chemical Engineering, University of California
, Berkeley, Berkeley, California,
USA
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Joint Graduate Program in Bioengineering, University of California Berkeley, Berkeley, California, and University of California San Francisco
, San Francisco, California,
USA
Department of Bioengineering, University of California
, Berkeley, Berkeley, California,
USA
Department of Chemical Engineering, University of California
, Berkeley, Berkeley, California,
USA
Search for other works by this author on:
Joint Graduate Program in Bioengineering, University of California Berkeley, Berkeley, California, and University of California San Francisco
, San Francisco, California,
USA
Department of Bioengineering, University of California
, Berkeley, Berkeley, California,
USA
Correspondence: Song Li, Ph.D., Department of Bioengineering, University of California, Berkeley, B108A Stanley Hall, Berkeley, CA 94720-1762. Telephone: (510) 666-2799; Fax: (510) 666-3381; e-mail [email protected]
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Accepted:
25 January 2010
Published:
09 February 2010
Cite
Kyle Kurpinski, Hayley Lam, Julia Chu, Aijun Wang, Ahra Kim, Eric Tsay, Smita Agrawal, David V. Schaffer, Song Li, Transforming Growth Factor-β and Notch Signaling Mediate Stem Cell Differentiation into Smooth Muscle Cells, Stem Cells, Volume 28, Issue 4, April 2010, Pages 734–742, https://doi.org/10.1002/stem.319
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Abstract
The differentiation of stem cells into smooth muscle cells (SMCs) plays an important role in vascular development and remodeling. In addition, stem cells represent a potential source of SMCs for regenerative medicine applications such as constructing vascular grafts. Previous studies have suggested that various biochemical factors, including transforming growth factor-β (TGF-β) and the Notch pathway, may play important roles in vascular differentiation. However, the interactions of these two signaling pathways in the differentiation of bone marrow mesenchymal stem cells (MSCs) have not been clearly defined. In this study, we profiled the gene expression in MSCs in response to TGF-β, and showed that TGF-β induced Notch ligand Jagged 1 (JAG1) and SMC markers, including smooth muscle α-actin (ACTA2), calponin 1 (CNN1), and myocardin (MYOCD), which were dependent on the activation of SMAD3 and Rho kinase. In addition, knocking down JAG1 expression partially blocked ACTA2 and CNN1 expression and completely blocked MYOCD expression, suggesting that JAG1 plays an important role in TGF-β-induced expression of SMC markers. On the other hand, the activation of Notch signaling induced the expression of SMC markers in MSCs and human embryonic stem cells (hESCs). Notch activation in hESCs also resulted in an increase of neural markers and a decrease of endothelial markers. These results suggest that Notch signaling mediates TGF-β regulation of MSC differentiation and that Notch signaling induces the differentiation of MSCs and hESCs into SMCs, which represents a novel mechanism involved in stem cell differentiation.
Copyright © 2010 AlphaMed Press
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