This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 94/9/1195    most recent 01.RES.0000126897.41658.81v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, S. Articles by Lechleider, R. J. Search for Related Content PubMed PubMed Citation Articles by Chen, S. Articles by Lechleider, R. J. Related Collections Cell biology/structural biology Cell signalling/signal transduction Smooth muscle proliferation and differentiation

Transforming Growth Factor-ß-Induced Differentiation of Smooth Muscle From a Neural Crest Stem Cell Line

From the Department of Cell Biology, Georgetown University Medical School, Washington, DC.

Correspondence to Robert J. Lechleider, Department of Cell Biology, Georgetown University Medical School, 3900 Reservoir Rd NW, Washington, DC 20057. E-mail RJL24{at}georgetown.edu

During vascular development, nascent endothelial networks are invested with a layer of supporting cells called pericytes in capillaries or smooth muscle in larger vessels. The cellular lineage of smooth muscle precursors and factors responsible for regulating their differentiation remain uncertain. In vivo, cells derived from the multipotent neural crest can give rise to vascular smooth muscle in parts of the head and also the cardiac outflow tract. Although transforming growth factor-ß (TGF-ß) has previously been shown to induce some smooth muscle markers from primary cultures of neural crest stem cells, the extent of the differentiation induced was not clear. In this study, we demonstrate that TGF-ß can induce many of the markers and characteristics of vascular smooth muscle from a neural crest stem cell line, Monc-1. Within 3 days of in vitro treatment, TGF-ß induces multiple smooth muscle-specific markers, while downregulating epithelial markers present on the parent cells. Treatment with TGF-ß also induces a contractile phenotype that responds to the muscarinic agonist carbachol and is not immediately reversed on TGF-ß withdrawal. Examination of the signaling pathways involved revealed that TGF-ß activation of Smad2 and Smad3 appear to be essential for the observed differentiation. Taken together, this system provides a novel model of smooth muscle differentiation that reliably recapitulates the process observed in vivo and allows for dissection of the pathways and processes involved in this process.

Key Words: smooth muscle • development • transforming growth factor-ß • Smad

This article has been cited by other articles:

				J. Y. Liu, H. F. Peng, and S. T. Andreadis Contractile smooth muscle cells derived from hair-follicle stem cells Cardiovasc Res, July 1, 2008; 79(1): 24 - 33. [Abstract] [Full Text] [PDF]

				S. Kennard, H. Liu, and B. Lilly Transforming Growth Factor- (TGF- 1) Down-regulates Notch3 in Fibroblasts to Promote Smooth Muscle Gene Expression J. Biol. Chem., January 18, 2008; 283(3): 1324 - 1333. [Abstract] [Full Text] [PDF]

				G. W. Calloni, C. Glavieux-Pardanaud, N. M. Le Douarin, and E. Dupin Sonic Hedgehog promotes the development of multipotent neural crest progenitors endowed with both mesenchymal and neural potentials PNAS, December 11, 2007; 104(50): 19879 - 19884. [Abstract] [Full Text] [PDF]

				C.-Q. Xie, J. Zhang, L. Villacorta, T. Cui, H. Huang, and Y. E. Chen A Highly Efficient Method to Differentiate Smooth Muscle Cells From Human Embryonic Stem Cells Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): e311 - e312. [Full Text] [PDF]

				V. Todorovic, D. Frendewey, D. E. Gutstein, Y. Chen, L. Freyer, E. Finnegan, F. Liu, A. Murphy, D. Valenzuela, G. Yancopoulos, et al. Long form of latent TGF-{beta} binding protein 1 (Ltbp1L) is essential for cardiac outflow tract septation and remodeling Development, October 15, 2007; 134(20): 3723 - 3732. [Abstract] [Full Text] [PDF]

				F. Li, Z. Luo, W. Huang, Q. Lu, C. S. Wilcox, P. A. Jose, and S. Chen Response Gene to Complement 32, a Novel Regulator for Transforming Growth Factor-beta-induced Smooth Muscle Differentiation of Neural Crest Cells J. Biol. Chem., April 6, 2007; 282(14): 10133 - 10137. [Abstract] [Full Text] [PDF]

				Q. Xiao, L. Zeng, Z. Zhang, Y. Hu, and Q. Xu Stem cell-derived Sca-1+ progenitors differentiate into smooth muscle cells, which is mediated by collagen IV-integrin {alpha}1/beta1/{alpha}v and PDGF receptor pathways Am J Physiol Cell Physiol, January 1, 2007; 292(1): C342 - C352. [Abstract] [Full Text] [PDF]

				H. Lindskog, E. Athley, E. Larsson, S. Lundin, M. Hellstrom, and P. Lindahl New Insights to Vascular Smooth Muscle Cell and Pericyte Differentiation of Mouse Embryonic Stem Cells In Vitro Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1457 - 1464. [Abstract] [Full Text] [PDF]

				S. Sinha, B. R. Wamhoff, M. H. Hoofnagle, J. Thomas, R. L. Neppl, T. Deering, B. P. Helmke, D. K. Bowles, A. V. Somlyo, and G. K. Owens Assessment of Contractility of Purified Smooth Muscle Cells Derived from Embryonic Stem Cells Stem Cells, July 1, 2006; 24(7): 1678 - 1688. [Abstract] [Full Text] [PDF]

				S. Chen, M. Crawford, R. M. Day, V. R. Briones, J. E. Leader, P. A. Jose, and R. J. Lechleider RhoA Modulates Smad Signaling during Transforming Growth Factor-beta-induced Smooth Muscle Differentiation J. Biol. Chem., January 20, 2006; 281(3): 1765 - 1770. [Abstract] [Full Text] [PDF]

				K. M. Howson, A. C. Aplin, M. Gelati, G. Alessandri, E. A. Parati, and R. F. Nicosia The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1396 - C1407. [Abstract] [Full Text] [PDF]

				G. Bergers and S. Song The role of pericytes in blood-vessel formation and maintenance Neuro-oncol, October 1, 2005; 7(4): 452 - 464. [Abstract] [PDF]

				T.-S. Li, M. Hayashi, H. Ito, A. Furutani, T. Murata, M. Matsuzaki, and K. Hamano Regeneration of Infarcted Myocardium by Intramyocardial Implantation of Ex Vivo Transforming Growth Factor-{beta}-Preprogrammed Bone Marrow Stem Cells Circulation, May 17, 2005; 111(19): 2438 - 2445. [Abstract] [Full Text] [PDF]

				H. Wurdak, L. M. Ittner, K. S. Lang, P. Leveen, U. Suter, J. A. Fischer, S. Karlsson, W. Born, and L. Sommer Inactivation of TGF{beta} signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome Genes & Dev., March 1, 2005; 19(5): 530 - 535. [Abstract] [Full Text] [PDF]

				R. L. C. Carvalho, L. Jonker, M.-J. Goumans, J. Larsson, P. Bouwman, S. Karlsson, P. t. Dijke, H. M. Arthur, and C. L. Mummery Defective paracrine signalling by TGF{beta} in yolk sac vasculature of endoglin mutant mice: a paradigm for hereditary haemorrhagic telangiectasia Development, December 15, 2004; 131(24): 6237 - 6247. [Abstract] [Full Text] [PDF]

				S. Sinha, M. H. Hoofnagle, P. A. Kingston, M. E. McCanna, and G. K. Owens Transforming growth factor-{beta}1 signaling contributes to development of smooth muscle cells from embryonic stem cells Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1560 - C1568. [Abstract] [Full Text] [PDF]