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Thromb Haemost 2010; 104(03): 440-448
DOI: 10.1160/TH09-11-0794
Theme Issue Article
Schattauer GmbH

The mechanism of stem cell differentiation into smooth muscle cells

Qingzhong Xiao
Cardiovascular Division, King’s College London BHF Centre, London, UK
,
Gang Wang
Cardiovascular Division, King’s College London BHF Centre, London, UK
,
Zhenling Luo
Cardiovascular Division, King’s College London BHF Centre, London, UK
,
Qingbo Xu
Cardiovascular Division, King’s College London BHF Centre, London, UK
› Author Affiliations
Further Information

Publication History

Received: 23 November 2009

Accepted after minor revision: 29 March 2010

Publication Date:
23 November 2017 (online)

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Summary

Stem cells represent one of the most promising areas in biological and medical research. All stem cells are defined as having two basic properties: unlimited self-renewal and the broad potential to differentiate in vitro, via ″progenitor cells″, into somatic cells of many tissue types, in which smooth muscle cell (SMC) differentiation is a complicated and not well defined process. It is known that serum response factors (SRF) and co-activator myocardin are essential transcription factors in SMC differentiation. Upstream activators or regulators for the transcription factors have been recently identified, such as reactive oxygen species, histone deacetylases, microRNAs and extracellular matrix (ECM) proteins and integrins. In this review we, therefore, aim to briefly summarise recent progress in the mechanism of stem cell differentiation into SMCs to highlight the potential targets for promoting/inhibiting SMC differentiation useful for vessel-tissue engineering and treatment of vascular disease.

Keywords

Stem cells - smooth muscle cells - differentiation - vascular disease
 

  • References

  • 1 Xiao Q, Roberts N, Jahangiri M, Xu Q. Stem Cells, Progenitor Cells and Vascular Diseases. Hauppauge NY: Nova Science Publishers, Inc; 2007. .
    Google Scholar
  • 2 Adams B, Xiao Q, Xu Q. Vascular progenitor cells and atherosclerosis. Future Cardiology 2007; 3: 635-645.
    CrossrefPubMedGoogle Scholar
  • 3 Adams B, Xiao Q, Xu Q. Stem cell therapy for vascular disease. Trends Cardiovasc Med 2007; 17: 246-251.
    CrossrefPubMedGoogle Scholar
  • 4 Xu Q. Stem cells and transplant arteriosclerosis. Circ Res 2008; 102: 1011-1024.
    CrossrefPubMedGoogle Scholar
  • 5 Poschl E, Schlotzer-Schrehardt U, Brachvogel B. et al. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development 2004; 131: 1619-1628.
    CrossrefPubMedGoogle Scholar
  • 6 Hutchings H, Ortega N, Plouet J. Extracellular matrix-bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation. Faseb J 2003; 17: 1520-1522.
    CrossrefPubMedGoogle Scholar
  • 7 Choy JC, Hung VH, Hunter AL. et al. Granzyme B induces smooth muscle cell apoptosis in the absence of perforin: involvement of extracellular matrix degradation. Arterioscler Thromb Vasc Biol 2004; 24: 2245-2250.
    CrossrefPubMedGoogle Scholar
  • 8 CJ Chien S, Bhatia SN. An extracellular matrix microarray for probing cellular differentiation. Nat Methods 2005; 2: 119-125.
    CrossrefPubMedGoogle Scholar
  • 9 Lozito TP, Taboas JM, Kuo CK. et al. Mesenchymal stem cell modification of endothelial matrix regulates their vascular differentiation. J Cell Biochem 2009; 107: 706-713.
    CrossrefPubMedGoogle Scholar
  • 10 Lozito TP, Kuo CK, Taboas JM. et al. Human mesenchymal stem cells express vascular cell phenotypes upon interaction with endothelial cell matrix. J Cell Biochem 2009; 107: 714-722.
    CrossrefPubMedGoogle Scholar
  • 11 Adiguzel E, Ahmad PJ, Franco C. et al. Collagens in the progression and complications of atherosclerosis. Vasc Med 2009; 14: 73-89.
    CrossrefPubMedGoogle Scholar
  • 12 Chen SS, Revoltella RP, Papini S. et al. Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems. Stem Cells 2003; 21: 281-295.
    CrossrefPubMedGoogle Scholar
  • 13 Kawasaki H, Suemori H, Mizuseki K. et al. Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci USA 2002; 99: 1580-1585.
    CrossrefPubMedGoogle Scholar
  • 14 Yamashita J, Itoh H, Hirashima M. et al. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 2000; 408: 92-96.
    CrossrefPubMedGoogle Scholar
  • 15 Sone M, Itoh H, Yamashita J. et al. Different differentiation kinetics of vascular progenitor cells in primate and mouse embryonic stem cells. Circulation 2003; 107: 2085-2088.
    CrossrefPubMedGoogle Scholar
  • 16 Sone M, Itoh H, Yamahara K. et al. Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration. Arterioscler Thromb Vasc Biol 2007; 27: 2127-2134.
    CrossrefPubMedGoogle Scholar
  • 17 Yamahara K, Sone M, Itoh H. et al. Augmentation of neovascularization [corrected] in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells. PLoS One 2008; 3: e1666.
    CrossrefPubMedGoogle Scholar
  • 18 Michelini M, Franceschini V, Sihui Chen S. et al. Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems. Cell Prolif 2006; 39: 217-229.
    CrossrefPubMedGoogle Scholar
  • 19 Xiao Q, Zeng L, Zhang Z. et al. 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 2007; 292: C342-C352.
    CrossrefPubMedGoogle Scholar
  • 20 Xiao Q, Zeng L, Zhang Z. et al. Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. Arterioscler Thromb Vasc Biol 2006; 26: 2244-2251.
    CrossrefPubMedGoogle Scholar
  • 21 Schober A, Knarren S, Lietz M. et al. Crucial role of stromal cell-derived factor-1alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation 2003; 108: 2491-2497.
    CrossrefPubMedGoogle Scholar
  • 22 Zernecke A, Schober A, Bot I. et al. SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res 2005; 96: 784-791.
    CrossrefPubMedGoogle Scholar
  • 23 Rupp PA, Little CD. Integrins in vascular development. Circ Res 2001; 89: 566-572.
    CrossrefPubMedGoogle Scholar
  • 24 Danen EH, Yamada KM. Fibronectin, integrins, and growth control. J Cell Physiol 2001; 189: 1-13.
    CrossrefPubMedGoogle Scholar
  • 25 Rohwedel J, Guan K, Zuschratter W. et al. Loss of beta1 integrin function results in a retardation of myogenic, but an acceleration of neuronal, differentiation of embryonic stem cells in vitro. Dev Biol 1998; 201: 167-184.
    CrossrefPubMedGoogle Scholar
  • 26 Lygoe KA, Norman JT, Marshall JF. et al. AlphaV integrins play an important role in myofibroblast differentiation. Wound Repair Regen 2004; 12: 461-470.
    CrossrefPubMedGoogle Scholar
  • 27 Deb A, Skelding KA, Wang S. et al. Integrin profile and in vivo homing of human smooth muscle progenitor cells. Circulation 2004; 110: 2673-2677.
    CrossrefPubMedGoogle Scholar
  • 28 Wu Y, Huang Y, Herring BP. et al. Integrin-linked kinase regulates smooth muscle differentiation marker gene expression in airway tissue. Am J Physiol Lung Cell Mol Physiol 2008; 295: L988-L997.
    CrossrefPubMedGoogle Scholar
  • 29 Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 2003; 42: 1075-1081.
    CrossrefPubMedGoogle Scholar
  • 30 Clempus RE, Griendling KK. Reactive oxygen species signaling in vascular smooth muscle cells. Cardiovasc Res 2006; 71: 216-225.
    CrossrefPubMedGoogle Scholar
  • 31 Su B, Mitra S, Gregg H. et al. Redox regulation of vascular smooth muscle cell differentiation. Circ Res 2001; 89: 39-46.
    CrossrefPubMedGoogle Scholar
  • 32 Lassegue B, Clempus RE. Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 2003; 285: R277-R297.
    CrossrefPubMedGoogle Scholar
  • 33 Touyz RM, Chen X, Tabet F. et al. Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: regulation by angiotensin II. Circ Res 2002; 90: 1205-1213.
    CrossrefPubMedGoogle Scholar
  • 34 Sumimoto H, Miyano K, Takeya R. Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem Biophys Res Commun 2005; 338: 677-686.
    CrossrefPubMedGoogle Scholar
  • 35 Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, Knaus UG. Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 2006; 18: 69-82.
    CrossrefPubMedGoogle Scholar
  • 36 Deliri H, McNamara CA. Nox 4 regulation of vascular smooth muscle cell differentiation marker gene expression. Arterioscler Thromb Vasc Biol 2007; 27: 12-14.
    CrossrefPubMedGoogle Scholar
  • 37 Szocs K, Lassegue B, Sorescu D. et al. Upregulation of Nox-based NAD(P)H oxidases in restenosis after carotid injury. Arterioscler Thromb Vasc Biol 2002; 22: 21-27.
    CrossrefPubMedGoogle Scholar
  • 38 Sorescu D, Weiss D, Lassegue B. et al. Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 2002; 105: 1429-1435.
    CrossrefPubMedGoogle Scholar
  • 39 Lassegue B, Sorescu D, Szocs K. et al. Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res 2001; 88: 888-894.
    CrossrefPubMedGoogle Scholar
  • 40 Clempus RE, Sorescu D, Dikalova AE. et al. Nox4 is required for maintenance of the differentiated vascular smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol 2007; 27: 42-48.
    CrossrefPubMedGoogle Scholar
  • 41 Xiao Q, Luo Z, Pepe AE. et al. Embryonic stem cell differentiation into smooth muscle cells is mediated by Nox4-produced H2O2. Am J Physiol Cell Physiol 2009; 296: C711-C723.
    CrossrefPubMedGoogle Scholar
  • 42 Lieb JD, Clarke ND. Control of transcription through intragenic patterns of nucleosome composition. Cell 2005; 123: 1187-1190.
    CrossrefPubMedGoogle Scholar
  • 43 Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 2005; 6: 838-849.
    CrossrefPubMedGoogle Scholar
  • 44 Mellor J. The dynamics of chromatin remodeling at promoters. Mol Cell 2005; 19: 147-157.
    CrossrefPubMedGoogle Scholar
  • 45 Backs J, Olson EN. Control of cardiac growth by histone acetylation/deacetylation. Circ Res 2006; 98: 15-24.
    PubMedGoogle Scholar
  • 46 de Ruijter AJ, van Gennip AH, Caron HN. et al. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003; 370: 737-749.
    CrossrefPubMedGoogle Scholar
  • 47 Gregoretti IV, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol 2004; 338: 17-31.
    CrossrefPubMedGoogle Scholar
  • 48 Witt O, Deubzer HE, Milde T. et al. HDAC family: What are the cancer relevant targets?. Cancer Lett 2009; 277: 8-21.
    CrossrefPubMedGoogle Scholar
  • 49 Fischle W, Kiermer V, Dequiedt F. et al. The emerging role of class II histone deacetylases. Biochem Cell Biol 2001; 79: 337-348.
    CrossrefPubMedGoogle Scholar
  • 50 Sengupta N, Seto E. Regulation of histone deacetylase activities. J Cell Biochem 2004; 93: 57-67.
    CrossrefPubMedGoogle Scholar
  • 51 Davis FJ, Gupta M, Camoretti-Mercado B. et al. Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy. J Biol Chem 2003; 278: 20047-20058.
    CrossrefPubMedGoogle Scholar
  • 52 Han A, He J, Wu Y. et al. Mechanism of recruitment of class II histone deacetylases by myocyte enhancer factor-2. J Mol Biol 2005; 345: 91-102.
    CrossrefPubMedGoogle Scholar
  • 53 Dressel U, Bailey PJ, Wang SC. et al. A dynamic role for HDAC7 in MEF2-mediated muscle differentiation. J Biol Chem 2001; 276: 17007-17013.
    CrossrefPubMedGoogle Scholar
  • 54 Kato H, Tamamizu-Kato S, Shibasaki F. Histone deacetylase 7 associates with hypoxia-inducible factor 1alpha and increases transcriptional activity. J Biol Chem 2004; 279: 41966-41974.
    CrossrefPubMedGoogle Scholar
  • 55 Sterner DE, Berger SL. Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 2000; 64: 435-459.
    CrossrefPubMedGoogle Scholar
  • 56 Chen J, Kitchen CM, Streb JW. et al. Myocardin: a component of a molecular switch for smooth muscle differentiation. J Mol Cell Cardiol 2002; 34: 1345-1356.
    CrossrefPubMedGoogle Scholar
  • 57 Wang Z, Wang DZ, Pipes GC. et al. Myocardin is a master regulator of smooth muscle gene expression. Proc Natl Acad Sci USA 2003; 100: 7129-7134.
    CrossrefPubMedGoogle Scholar
  • 58 Wang Z, Wang DZ, Hockemeyer D. et al. Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression. Nature 2004; 428: 185-189.
    CrossrefPubMedGoogle Scholar
  • 59 Margariti A, Xiao Q, Zampetaki A. et al. Splicing of HDAC7 modulates the SRFmyocardin complex during stem-cell differentiation towards smooth muscle cells. J Cell Sci 2009; 122: 460-470.
    CrossrefPubMedGoogle Scholar
  • 60 Waltregny D, Glenisson W, Tran SL. et al. Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility. Faseb J 2005; 19: 966-968.
    CrossrefPubMedGoogle Scholar
  • 61 Waltregny D, De Leval L, Glenisson W. et al. Expression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues. Am J Pathol 2004; 165: 553-564.
    CrossrefPubMedGoogle Scholar
  • 62 McDonald OG, Owens GK. Programming smooth muscle plasticity with chromatin dynamics. Circ Res 2007; 100: 1428-1441.
    CrossrefPubMedGoogle Scholar
  • 63 McDonald OG, Wamhoff BR, Hoofnagle MH. et al. Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo. J Clin Invest 2006; 116: 36-48.
    PubMedGoogle Scholar
  • 64 Yoshida T, Gan Q, Owens GK. Kruppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids. Am J Physiol Cell Physiol 2008; 295: C1175-C1182.
    CrossrefPubMedGoogle Scholar
  • 65 Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993; 75: 855-862.
    CrossrefPubMedGoogle Scholar
  • 66 Wightman B, Burglin TR, Gatto J. et al. Negative regulatory sequences in the lin-14 3‘-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development. Genes Dev 1991; 5: 1813-1824.
    CrossrefPubMedGoogle Scholar
  • 67 Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-297.
    CrossrefPubMedGoogle Scholar
  • 68 Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science 2007; 318: 1931-1934.
    CrossrefPubMedGoogle Scholar
  • 69 Vasudevan S, Tong Y, Steitz JA. Cell-cycle control of microRNA-mediated translation regulation. Cell Cycle 2008; 7: 1545-1549.
    CrossrefPubMedGoogle Scholar
  • 70 Bonauer A, Carmona G, Iwasaki M. et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 2009; 324: 1710-1713.
    CrossrefPubMedGoogle Scholar
  • 71 Cordes KR, Srivastava D. MicroRNA regulation of cardiovascular development. Circ Res 2009; 104: 724-732.
    CrossrefPubMedGoogle Scholar
  • 72 Ren XP, Wu J, Wang X. et al. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation 2009; 119: 2357-2366.
    CrossrefPubMedGoogle Scholar
  • 73 Suarez Y, Sessa WC. MicroRNAs as novel regulators of angiogenesis. Circ Res 2009; 104: 442-454.
    CrossrefPubMedGoogle Scholar
  • 74 Oberdoerffer P, Kanellopoulou C, Heissmeyer V. et al. Efficiency of RNA interference in the mouse hematopoietic system varies between cell types and developmental stages. Mol Cell Biol 2005; 25: 3896-3905.
    CrossrefPubMedGoogle Scholar
  • 75 Murchison EP, Partridge JF, Tam OH. et al. Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci USA 2005; 102: 12135-12140.
    CrossrefPubMedGoogle Scholar
  • 76 Wang Y, Medvid R, Melton C. et al. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet 2007; 39: 380-385.
    CrossrefPubMedGoogle Scholar
  • 77 Ivey KN, Muth A, Arnold J. et al. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell 2008; 2: 219-229.
    CrossrefPubMedGoogle Scholar
  • 78 Kwon C, Han Z, Olson EN. et al. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci USA 2005; 102: 18986-18991.
    CrossrefPubMedGoogle Scholar
  • 79 Zhao Y, Ransom JF, Li A. et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1–2. Cell 2007; 129: 303-317.
    CrossrefPubMedGoogle Scholar
  • 80 Rao PK, Kumar RM, Farkhondeh M. et al. Myogenic factors that regulate expression of muscle-specific microRNAs. Proc Natl Acad Sci USA 2006; 103: 8721-8726.
    CrossrefPubMedGoogle Scholar
  • 81 Cordes KR, Sheehy NT, White MP. et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 2009; 460: 705-710.
    PubMedGoogle Scholar
  • 82 Xu N, Papagiannakopoulos T, Pan G. et al. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 2009; 137: 647-658.
    CrossrefPubMedGoogle Scholar
  • 83 Xin M, Small EM, Sutherland LB. et al. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev 2009; 23: 2166-2178.
    CrossrefPubMedGoogle Scholar
  • 84 Boettger T, Beetz N, Kostin S. et al. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest 2009; 119: 2634-2647.
    CrossrefPubMedGoogle Scholar
  • 85 Kuhn AR, Schlauch K, Lao R. et al. MicroRNA Expression in Human Airway Smooth Muscle Cells: Role of miR-25 in Regulation of Airway Smooth Muscle Phenotype. Am J Respir Cell Mol Biol 2010; 42: 506-513.
    CrossrefPubMedGoogle Scholar
  • 86 Davis BN, Hilyard AC, Nguyen PH. et al. Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype. J Biol Chem 2009; 284: 3728-3738.
    CrossrefPubMedGoogle Scholar