Table of Contents Author Guidelines Submit a Manuscript
Stem Cells International
Volume 2015 (2015), Article ID 468428, 16 pages
http://dx.doi.org/10.1155/2015/468428
Review Article

Hedgehog and Resident Vascular Stem Cell Fate

1Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin 9, Ireland
2School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin 9, Ireland
3Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA

Received 15 January 2015; Accepted 1 April 2015

Academic Editor: Qingzhong Xiao

Copyright © 2015 Ciaran J. Mooney et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. J. Lavine, F. Long, K. Choi, C. Smith, and D. M. Ornitz, “Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development,” Development, vol. 135, no. 18, pp. 3161–3171, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. R. Pola, L. E. Ling, T. R. Aprahamian et al., “Postnatal recapitulation of embryonic hedgehog pathway in response to skeletal muscle ischemia,” Circulation, vol. 108, no. 4, pp. 479–485, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. R. Pola, L. E. Ling, M. Silver et al., “The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors,” Nature Medicine, vol. 7, no. 6, pp. 706–711, 2001. View at Google Scholar · View at Scopus
  4. K. Ray, “Infection: activation of Hedgehog pathway promotes fibrogenesis and vascular remodelling in human schistosomiasis,” Nature Reviews Gastroenterology and Hepatology, vol. 9, article 689, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. C. M. Moran, M. C. Salanga, and P. A. Krieg, “Hedgehog signaling regulates size of the dorsal aortae and density of the plexus during avian vascular development,” Developmental Dynamics, vol. 240, no. 6, pp. 1354–1364, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. J. N. Passman, X. R. Dong, S.-P. Wu et al., “A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 27, pp. 9349–9354, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Morrow, J. P. Cullen, W. Liu et al., “Sonic hedgehog induces notch target gene expression in vascular smooth muscle cells via VEGF-A,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 7, pp. 1112–1118, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. E. M. Redmond, K. Hamm, J. P. Cullen, E. Hatch, P. A. Cahill, and D. Morrow, “Inhibition of patched-1 prevents injury-induced neointimal hyperplasia,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 8, pp. 1960–1964, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. D. Morrow, S. Guha, C. Sweeney et al., “Notch and vascular smooth muscle cell phenotype,” Circulation Research, vol. 103, no. 12, pp. 1370–1382, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. F. A. High, M. Zhang, A. Proweller et al., “An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation,” Journal of Clinical Investigation, vol. 117, no. 2, pp. 353–363, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. F. A. High, M. L. Min, W. S. Pear, K. M. Loomes, K. H. Kaestner, and J. A. Epstein, “Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 6, pp. 1955–1959, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. D. Morrow, A. Scheller, Y. A. Birney et al., “Notch-mediated CBF-1/RBP-Jκ-dependent regulation of human vascular smooth muscle cell phenotype in vitro,” The American Journal of Physiology—Cell Physiology, vol. 289, no. 5, pp. C1188–C1196, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Sweeney, D. Morrow, Y. A. Birney et al., “Notch 1 and 3 receptor signaling modulates vascular smooth muscle cell growth, apoptosis, and migration via a CBF-1/RBP-Jk dependent pathway,” The FASEB Journal, vol. 18, no. 12, pp. 1421–1423, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. E. M. Redmond, W. Liu, K. Hamm, E. Hatch, P. A. Cahill, and D. Morrow, “Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling,” PLoS ONE, vol. 9, no. 1, Article ID e84122, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. S. L. Siggins, N.-Y. N. Nguyen, M. P. McCormack et al., “The Hedgehog receptor Patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms,” Blood, vol. 114, no. 5, pp. 995–1004, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Huang and D. Kalderon, “Coupling of Hedgehog and Hippo pathways promotes stem cell maintenance by stimulating proliferation,” Journal of Cell Biology, vol. 205, no. 3, pp. 325–338, 2014. View at Publisher · View at Google Scholar · View at Scopus
  17. N. F. Worth, B. E. Rolfe, J. Song, and G. R. Campbell, “Vascular smooth muscle cell phenotypic modulation in culture is associated with reorganisation of contractile and cytoskeletal proteins,” Cell Motility and the Cytoskeleton, vol. 49, no. 3, pp. 130–145, 2001. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Li, S. Sims, Y. Jiao, L. H. Chow, and J. G. Pickering, “Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes,” Circulation Research, vol. 85, no. 4, pp. 338–348, 1999. View at Publisher · View at Google Scholar · View at Scopus
  19. Z. Tang, A. Wang, F. Yuan et al., “Differentiation of multipotent vascular stem cells contributes to vascular diseases,” Nature Communications, vol. 3, article 875, 2012. View at Google Scholar · View at Scopus
  20. C. Nüsslein-Volhard and E. Wieschaus, “Mutations affecting segment number and polarity in Drosophila,” Nature, vol. 287, no. 5785, pp. 795–801, 1980. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Gallet, “Hedgehog morphogen: from secretion to reception,” Trends in Cell Biology, vol. 21, no. 4, pp. 238–246, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Briscoe and P. P. Thérond, “The mechanisms of Hedgehog signalling and its roles in development and disease,” Nature Reviews Molecular Cell Biology, vol. 14, no. 7, pp. 416–429, 2013. View at Google Scholar · View at Scopus
  23. V. L. Horner and T. Caspary, “Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13bhnn stems from abnormal Shh signaling,” Developmental Biology, vol. 355, no. 1, pp. 43–54, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. K. K. Mak, H. M. Kronenberg, P.-T. Chuang, S. Mackem, and Y. Yang, “Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy,” Development, vol. 135, no. 11, pp. 1947–1956, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. I. B. Barsoum, J. Kaur, R. S. Ge, P. S. Cooke, and H. H.-C. Yao, “Dynamic changes in fetal Leydig cell populations influence adult Leydig cell populations in mice,” The FASEB Journal, vol. 27, no. 7, pp. 2657–2666, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. K. F. Liem Jr., M. He, P. J. R. Ocbina, and K. V. Anderson, “Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 32, pp. 13377–13382, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Chen, N. Sasai, G. Ma et al., “Sonic Hedgehog dependent phosphorylation by CK1α and GRK2 is required for ciliary accumulation and activation of smoothened,” PLoS Biology, vol. 9, no. 6, Article ID e1001083, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. C.-W. Fan, B. Chen, I. Franco et al., “The Hedgehog Pathway Effector Smoothened Exhibits Signaling Competency in the Absence of Ciliary Accumulation,” Chemistry & Biology, vol. 21, no. 12, pp. 1680–1689, 2014. View at Publisher · View at Google Scholar
  29. J. Taipale, M. K. Cooper, T. Maiti, and P. A. Beachy, “Patched acts catalytically to suppress the activity of smoothened,” Nature, vol. 418, no. 6900, pp. 892–897, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Nachtergaele, L. K. Mydock, K. Krishnan et al., “Oxysterols are allosteric activators of the oncoprotein Smoothened,” Nature Chemical Biology, vol. 8, no. 2, pp. 211–220, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. C.-C. Hui, D. Slusarski, K. A. Platt, R. Holmgren, and A. L. Joyner, “Expression of three mouse homologs of the drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm-and mesoderm-derived tissues suggests multiple roles during postimplantation development,” Developmental Biology, vol. 162, no. 2, pp. 402–413, 1994. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Bowers, L. Eng, Z. Lao et al., “Limb anterior-posterior polarity integrates activator and repressor functions of GLI2 as well as GLI3,” Developmental Biology, vol. 370, no. 1, pp. 110–124, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. N. Bhatia, S. Thiyagarajan, I. Elcheva et al., “Gli2 is targeted for ubiquitination and degradation by β-TrCP ubiquitin ligase,” The Journal of Biological Chemistry, vol. 281, no. 28, pp. 19320–19326, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. P. K. Dhanyamraju, P. S. Holz, F. Finkernagel, V. Fendrich, and M. Lauth, “Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway,” Molecular Cancer Therapeutics, vol. 14, no. 3, pp. 727–739, 2015. View at Publisher · View at Google Scholar
  35. N. A. Riobo, G. M. Haines, and C. P. Emerson Jr., “Protein kinase C-delta and mitogen-activated protein/extracellular signal-regulated kinase-1 control GLI activation in hedgehog signaling,” Cancer Research, vol. 66, no. 2, pp. 839–845, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. P. Chinchilla, L. Xiao, M. G. Kazanietz, and N. A. Riobo, “Hedgehog proteins activate pro-angiogenic responses in endothelial cells through non-canonical signaling pathways,” Cell Cycle, vol. 9, no. 3, pp. 570–579, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. A. H. Polizio, P. Chinchilla, X. Chen, D. R. Manning, and N. A. Riobo, “Sonic Hedgehog activates the GTPases Rac1 and RhoA in a Gli-independent manner through coupling of smoothened to Gi proteins,” Science Signaling, vol. 4, no. 200, article pt7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Guo, J. Gao, Z. Li et al., “Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo,” Cancer Letters, vol. 339, no. 2, pp. 185–194, 2013. View at Publisher · View at Google Scholar · View at Scopus
  39. J. E. Fish and J. D. Wythe, “The molecular regulation of arteriovenous specification and maintenance,” Developmental Dynamics, vol. 244, no. 3, pp. 391–409, 2015. View at Publisher · View at Google Scholar
  40. M.-A. Renault, C. Chapouly, Q. Yao et al., “Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival,” Circulation Research, vol. 112, no. 5, pp. 762–770, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. N. D. Lawson, N. Scheer, V. N. Pham et al., “Notch signaling is required for arterial-venous differentiation during embryonic vascular development,” Development, vol. 128, no. 19, pp. 3675–3683, 2001. View at Google Scholar · View at Scopus
  42. N. Villa, L. Walker, C. E. Lindsell, J. Gasson, M. L. Iruela-Arispe, and G. Weinmaster, “Vascular expression of Notch pathway receptors and ligands is restricted to arterial vessels,” Mechanisms of Development, vol. 108, no. 1-2, pp. 161–164, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. H. Huang, J. L. Cotton, Y. Wang et al., “Specific requirement of Gli transcription factors in hedgehog-mediated intestinal development,” Journal of Biological Chemistry, vol. 288, no. 24, pp. 17589–17596, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. C. Gutiérrez-Frías, R. Sacedón, C. Hernández-López et al., “Sonic hedgehog regulates early human thymocyte differentiation by counteracting the IL-7-induced development of CD34+ precursor cells,” The Journal of Immunology, vol. 173, no. 8, pp. 5046–5053, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. J.-X. Zhou, L.-W. Jia, W.-M. Liu et al., “Role of sonic hedgehog in maintaining a pool of proliferating stem cells in the human fetal epidermis,” Human Reproduction, vol. 21, no. 7, pp. 1698–1704, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. A. Wabik and P. H. Jones, “Switching roles: the functional plasticity of adult tissue stem cells,” The EMBO Journal, 2015. View at Publisher · View at Google Scholar
  47. C. D. Peacock, Q. Wang, G. S. Gesell et al., “Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 10, pp. 4048–4053, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. S. Liu, G. Dontu, I. D. Mantle et al., “Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells,” Cancer Research, vol. 66, no. 12, pp. 6063–6071, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Mathieu, Z. Zhang, A. Nelson et al., “Hypoxia induces re-entry of committed cells into pluripotency,” Stem Cells, vol. 31, no. 9, pp. 1737–1748, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. C. M. Martin, A. Ferdous, T. Gallardo et al., “Hypoxia-inducible factor-2α transactivates Abcg2 and promotes cytoprotection in cardiac side population cells,” Circulation Research, vol. 102, no. 9, pp. 1075–1081, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. C. M. F. Potter, K. H. Lao, L. Zeng, and Q. Xu, “Role of biomechanical forces in stem cell vascular lineage differentiation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 34, no. 10, pp. 2184–2190, 2014. View at Publisher · View at Google Scholar
  52. A. J. Wagers, “The stem cell niche in regenerative medicine,” Cell Stem Cell, vol. 10, no. 4, pp. 362–369, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. D. Morrow, C. Sweeney, Y. A. Birney et al., “Biomechanical regulation of hedgehog signaling in vascular smooth muscle cells in vitro and in vivo,” The American Journal of Physiology—Cell Physiology, vol. 292, no. 1, pp. C488–C496, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. E. M. Surace, K. S. Balaggan, A. Tessitore et al., “Inhibition of ocular neovascularization by Hedgehog blockade,” Molecular Therapy, vol. 13, no. 3, pp. 573–579, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. E. Dohle, S. Fuchs, M. Kolbe, A. Hofmann, H. Schmidt, and C. J. Kirkpatrick, “Comparative study assessing effects of sonic hedgehog and VEGF in a human co-culture model for bone vascularisation strategies,” European Cells and Materials, vol. 21, pp. 144–156, 2011. View at Google Scholar · View at Scopus
  56. F. Li, M. Duman-Scheel, D. Yang et al., “Sonic hedgehog signaling induces vascular smooth muscle cell proliferation via induction of the G1 cyclin-retinoblastoma axis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 9, pp. 1787–1794, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. G. Wang, Z. Zhang, Z. Xu et al., “Activation of the sonic hedgehog signaling controls human pulmonary arterial smooth muscle cell proliferation in response to hypoxia,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1803, no. 12, pp. 1359–1367, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. Q. Yao, M.-A. Renault, C. Chapouly et al., “Sonic hedgehog mediates a novel pathway of PDGF-BB-dependent vessel maturation.,” Blood, vol. 123, no. 15, pp. 2429–2437, 2014. View at Publisher · View at Google Scholar · View at Scopus
  59. J.-R. Fu, W.-L. Liu, J.-F. Zhou et al., “Sonic hedgehog protein promotes bone marrow-derived endothelial progenitor cell proliferation, migration and VEGF production via PI 3-kinase/Akt signaling pathways,” Acta Pharmacologica Sinica, vol. 27, no. 6, pp. 685–693, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. F.-H. Li, S.-J. Xin, S.-Y. Zhang et al., “The sonic hedgehog induce vascular adventitial fibroblasts phenotypic modulation, proliferation and migration,” Zhonghua Yi Xue Za Zhi, vol. 89, no. 43, pp. 3079–3082, 2009. View at Google Scholar · View at Scopus
  61. U. Tigges, M. Komatsu, and W. B. Stallcup, “Adventitial pericyte progenitor/mesenchymal stem cells participate in the restenotic response to arterial injury,” Journal of Vascular Research, vol. 50, no. 2, pp. 134–144, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. T. Yamashima, A. B. Tonchev, I. H. Vachkov et al., “Vascular adventitia generates neuronal progenitors in the monkey hippocampus after ischemia,” Hippocampus, vol. 14, no. 7, pp. 861–875, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. M. W. Majesky, X. R. Dong, V. Hoglund, G. Daum, and W. M. Mahoney Jr., “The adventitia: a progenitor cell niche for the vessel wall,” Cells Tissues Organs, vol. 195, no. 1-2, pp. 73–81, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. D. Pinto, A. Gregorieff, H. Begthel, and H. Clevers, “Canonical Wnt signals are essential for homeostasis of the intestinal epithelium,” Genes and Development, vol. 17, no. 14, pp. 1709–1713, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Aguirre, M. E. Rubio, and V. Gallo, “Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal,” Nature, vol. 467, no. 7313, pp. 323–327, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. B. Dudley, C. Palumbo, J. Nalepka, and K. Molyneaux, “BMP signaling controls formation of a primordial germ cell niche within the early genital ridges,” Developmental Biology, vol. 343, no. 1-2, pp. 84–93, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Hu, Z. Zhang, E. Torsney et al., “Abundant progenitor cells in the adventitia contribute to atheroscleroses of vein grafts in ApoE-deficient mice,” The Journal of Clinical Investigation, vol. 113, no. 9, pp. 1258–1265, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. Y. Tintut, Z. Alfonso, T. Saini et al., “Multilineage potential of cells from the artery wall,” Circulation, vol. 108, no. 20, pp. 2505–2510, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. M. Crisan, S. Yap, L. Casteilla et al., “A perivascular origin for mesenchymal stem cells in multiple human organs,” Cell Stem Cell, vol. 3, no. 3, pp. 301–313, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. T.-N. Tsai, J. P. Kirton, P. Campagnolo et al., “Contribution of stem cells to neointimal formation of decellularized vessel grafts in a novel mouse model,” The American Journal of Pathology, vol. 181, no. 1, pp. 362–373, 2012. View at Publisher · View at Google Scholar · View at Scopus
  71. D. T. Covas, C. E. Piccinato, M. D. Orellana et al., “Mesenchymal stem cells can be obtained from the human saphena vein,” Experimental Cell Research, vol. 309, no. 2, pp. 340–344, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. C. E. Murry, C. T. Gipaya, T. Bartosek, E. P. Benditt, and S. M. Schwartz, “Monoclonality of smooth muscle cells in human atherosclerosis,” The American Journal of Pathology, vol. 151, no. 3, pp. 697–706, 1997. View at Google Scholar · View at Scopus
  73. J. Sainz, “Isolation of ‘Side Population’ progenitor cells from healthy arteries of adult mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, pp. 281–286, 2005. View at Google Scholar
  74. M. Sata, A. Saiura, A. Kunisato et al., “Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis,” Nature Medicine, vol. 8, no. 4, pp. 403–409, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. H. Iwata, I. Manabe, and R. Nagai, “Lineage of bone marrow-derived cells in atherosclerosis,” Circulation Research, vol. 112, no. 12, pp. 1634–1647, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Iwata, I. Manabe, K. Fujiu et al., “Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages,” Circulation, vol. 122, no. 20, pp. 2048–2057, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. P. Campagnolo, D. Cesselli, A. A.-L. Zen et al., “Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential,” Circulation, vol. 121, no. 15, pp. 1735–1745, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. E. Zengin, F. Chalajour, U. M. Gehling et al., “Vascular wall resident progenitor cells: a source for postnatal vasculogenesis,” Development, vol. 133, no. 8, pp. 1543–1551, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. D. Klein, P. Weißhardt, V. Kleff, H. Jastrow, H. G. Jakob, and S. Ergün, “Vascular wall-resident CD44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation,” PLoS ONE, vol. 6, no. 5, Article ID e20540, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. D. Klein, M. Benchellal, V. Kleff, H. G. Jakob, and S. Ergün, “Hox genes are involved in vascular wall-resident multipotent stem cell differentiation into smooth muscle cells,” Scientific Reports, vol. 3, article 2178, 2013. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Krause, Y. Xu, J. Joh et al., “Overexpression of sonic hedgehog in the lung mimics the effect of lung injury and compensatory lung growth on pulmonary Sca-1 and CD34 positive cells,” Molecular Therapy, vol. 18, no. 2, pp. 404–412, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. J. J. Trowbridge, M. P. Scott, and M. Bhatia, “Hedgehog modulates cell cycle regulators in stem cells to control hematopoietic regeneration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 38, pp. 14134–14139, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. C. Fontaine, W. Cousin, M. Plaisant, C. Dani, and P. Peraldi, “Hedgehog signaling alters adipocyte maturation of human mesenchymal stem cells,” Stem Cells, vol. 26, no. 4, pp. 1037–1046, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. I.-S. Hong and K.-S. Kang, “The effects of Hedgehog on the RNA-binding protein Msi1 in the proliferation and apoptosis of mesenchymal stem cells,” PLoS ONE, vol. 8, no. 2, Article ID e56496, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. T. L. B. Spitzer, A. Rojas, Z. Zelenko et al., “Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype,” Biology of Reproduction, vol. 86, no. 2, article 58, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. A. F. Steinert, M. Weissenberger, M. Kunz et al., “Indian hedgehog gene transfer is a chondrogenic inducer of human mesenchymal stem cells,” Arthritis Research and Therapy, vol. 14, no. 4, article R168, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. C. Holmes and W. L. Stanford, “Concise review: stem cell antigen-1: expression, function, and enigma,” Stem Cells, vol. 25, no. 6, pp. 1339–1347, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. B. Holifield, T. Helgason, S. Jemelka et al., “Differentiated vascular myocytes: are they involved in neointimal formation?” Journal of Clinical Investigation, vol. 97, no. 3, pp. 814–825, 1996. View at Publisher · View at Google Scholar · View at Scopus
  89. D. Gomez, L. S. Shankman, A. T. Nguyen, and G. K. Owens, “Detection of histone modifications at specific gene loci in single cells in histological sections,” Nature Methods, vol. 10, no. 2, pp. 171–177, 2013. View at Publisher · View at Google Scholar · View at Scopus
  90. H.-Z. Bai, J. Masuda, Y. Sawa et al., “Neointima formation after vascular stent implantation. Spatial and chronological distribution of smooth muscle cell proliferation and phenotypic modulation,” Arteriosclerosis and Thrombosis, vol. 14, no. 11, pp. 1846–1853, 1994. View at Publisher · View at Google Scholar · View at Scopus
  91. E.-I. Okamoto, T. Suzuki, M. Aikawa et al., “Diversity of the synthetic-state smooth-muscle cells proliferating in mechanically and hemodynamically injured rabbit arteries,” Laboratory Investigation, vol. 74, no. 1, pp. 120–128, 1996. View at Google Scholar · View at Scopus
  92. R. A. Nemenoff, H. Horita, A. C. Ostriker et al., “SDF-1α induction in mature smooth muscle cells by inactivation of PTEN is a critical mediator of exacerbated injury-induced neointima formation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 6, pp. 1300–1308, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. B. Herring, A. M. Hoggatt, C. Burlak, and S. Offermanns, “Previously differentiated medial vascular smooth muscle cells contribute to neointima formation following vascular injury,” Vascular Cell, vol. 6, no. 1, article 21, 2014. View at Publisher · View at Google Scholar
  94. A. L. Firth, W. Yao, A. Ogawa, M. M. Madani, G. Y. Lin, and J. X.-J. Yuan, “Multipotent mesenchymal progenitor cells are present in endarterectomized tissues from patients with chronic thromboembolic pulmonary hypertension,” The American Journal of Physiology—Cell Physiology, vol. 298, no. 5, pp. C1217–C1225, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. Z. Tang, A. Wang, D. Wang, and S. Li, “Smooth muscle cells: to be or not to be? Response to Nguyen et al,” Circulation research, vol. 112, no. 1, pp. 23–26, 2013. View at Publisher · View at Google Scholar · View at Scopus
  96. E. Kennedy, R. Hakimjavadi, C. Greene et al., “Embryonic rat vascular smooth muscle cells revisited—a model for neonatal, neointimal SMC or differentiated vascular stem cells?” Vascular Cell, vol. 6, no. 1, article 6, 2014. View at Publisher · View at Google Scholar · View at Scopus
  97. E. Kennedy, C. J. Mooney, R. Hakimjavadi et al., “Adult vascular smooth muscle cells in culture express neural stem cell markers typical of resident multipotent vascular stem cells,” Cell and Tissue Research, vol. 358, no. 1, pp. 203–216, 2014. View at Publisher · View at Google Scholar
  98. J.-I. Kawabe and N. Hasebe, “Role of the vasa vasorum and vascular resident stem cells in atherosclerosis,” BioMed Research International, vol. 2014, Article ID 701571, 8 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  99. J. N. Regan, Regulation of adventitia-resident progenitor cells [Ph.D. dissertation], 2010.
  100. M. Wan, C. Li, G. Zhen et al., “Injury-activated transforming growth factor β controls mobilization of mesenchymal stem cells for tissue remodeling,” Stem Cells, vol. 30, no. 11, pp. 2498–2511, 2012. View at Publisher · View at Google Scholar · View at Scopus
  101. J. X. Rong, M. Shapiro, E. Trogan, and E. A. Fisher, “Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 23, pp. 13531–13536, 2003. View at Publisher · View at Google Scholar · View at Scopus
  102. P. Ciceri, E. Volpi, I. Brenna et al., “Combined effects of ascorbic acid and phosphate on rat VSMC osteoblastic differentiation,” Nephrology Dialysis Transplantation, vol. 27, no. 1, pp. 122–127, 2012. View at Publisher · View at Google Scholar · View at Scopus
  103. D. C. Graves and Z. Yablonka-Reuveni, “Vascular smooth muscle cells spontaneously adopt a skeletal muscle phenotype: a unique Myf5-/MyoD+ myogenic program,” Journal of Histochemistry & Cytochemistry, vol. 48, no. 9, pp. 1173–1193, 2000. View at Publisher · View at Google Scholar
  104. X.-B. Liao, Z.-Y. Zhang, K. Yuan et al., “MiR-133a modulates osteogenic differentiation of vascular smooth muscle cells,” Endocrinology, vol. 154, no. 9, pp. 3344–3352, 2013. View at Publisher · View at Google Scholar · View at Scopus
  105. A. Bukovsky, “Sex steroid-mediated reprogramming of vascular smooth muscle cells to stem cells and neurons: possible utilization of sex steroid combinations for regenerative treatment without utilization of in vitro developed stem cells,” Cell Cycle, vol. 8, no. 24, pp. 4079–4084, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. X. Shi, D. DiRenzo, L.-W. Guo et al., “TGF-β/Smad3 stimulates stem cell/developmental gene expression and vascular smooth muscle cell de-differentiation,” PLoS ONE, vol. 9, no. 4, Article ID e93995, 2014. View at Publisher · View at Google Scholar · View at Scopus
  107. S. Kasper, “Exploring the origins of the normal prostate and prostate cancer stem cell,” Stem Cell Reviews, vol. 4, no. 3, pp. 193–201, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. K. Kurpinski, H. Lam, J. Chu et al., “Transforming growth factor-β and notch signaling mediate stem cell differentiation into smooth muscle cells,” Stem Cells, vol. 28, no. 4, pp. 734–742, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. X. Li, J. Chu, A. Wang et al., “Uniaxial mechanical strain modulates the differentiation of neural crest stem cells into smooth muscle lineage on micropatterned surfaces,” PLoS ONE, vol. 6, no. 10, Article ID e26029, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. S.-W. Lee, M. A. Moskowitz, and J. R. Sims, “Sonic hedgehog inversely regulates the expression of angiopoietin-1 and angiopoietin-2 in fibroblasts,” International Journal of Molecular Medicine, vol. 19, no. 3, pp. 445–451, 2007. View at Google Scholar · View at Scopus
  111. N. Byrd, S. Becker, P. Maye et al., “Hedgehog is required for murine yolk sac angiogenesis,” Development, vol. 129, no. 2, pp. 361–372, 2002. View at Google Scholar · View at Scopus
  112. R. Scatena, P. Bottoni, A. Pontoglio, and B. Giardina, “Cancer stem cells: the development of new cancer therapeutics,” Expert Opinion on Biological Therapy, vol. 11, no. 7, pp. 875–892, 2011. View at Publisher · View at Google Scholar · View at Scopus
  113. J.-M. Daniel, W. Bielenberg, P. Stieger, S. Weinert, H. Tillmanns, and D. G. Sedding, “Time-course analysis on the differentiation of bone marrow-derived progenitor cells into smooth muscle cells during neointima formation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 10, pp. 1890–1896, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. P. Zerr, K. Palumbo-Zerr, A. Distler et al., “Inhibition of hedgehog signaling for the treatment of murine sclerodermatous chronic graft-versus-host disease,” Blood, vol. 120, no. 14, pp. 2909–2917, 2012. View at Publisher · View at Google Scholar · View at Scopus
  115. H. Li, J. Li, Y. Li et al., “Sonic hedgehog promotes autophagy of vascular smooth muscle cells,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 303, no. 11, pp. H1319–H1331, 2012. View at Publisher · View at Google Scholar · View at Scopus
  116. Y. Li, K. Takeshita, P.-Y. Liu et al., “Smooth muscle notch1 mediates neointimal formation after vascular injury,” Circulation, vol. 119, no. 20, pp. 2686–2692, 2009. View at Publisher · View at Google Scholar · View at Scopus
  117. J. Roncalli, M.-A. Renault, J. Tongers et al., “Sonic hedgehog-induced functional recovery after myocardial infarction is enhanced by AMD3100-mediated progenitor-cell mobilization,” Journal of the American College of Cardiology, vol. 57, no. 24, pp. 2444–2452, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. L. Beckers, S. Heeneman, L. Wang et al., “Disruption of hedgehog signalling in ApoE-/- mice reduces plasma lipid levels, but increases atherosclerosis due to enhanced lipid uptake by macrophages,” Journal of Pathology, vol. 212, no. 4, pp. 420–428, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. J. Chen, A. Crabbe, V. van Duppen, and H. Vankelecom, “The notch signaling system is present in the postnatal pituitary: marked expression and regulatory activity in the newly discovered side population,” Molecular Endocrinology, vol. 20, no. 12, pp. 3293–3307, 2006. View at Publisher · View at Google Scholar · View at Scopus
  120. L. Chang, M. Noseda, M. Higginson et al., “Differentiation of vascular smooth muscle cells from local precursors during embryonic and adult arteriogenesis requires Notch signaling,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 18, pp. 6993–6998, 2012. View at Publisher · View at Google Scholar · View at Scopus
  121. Y. Sato, T. Watanabe, D. Saito et al., “Notch mediates the segmental specification of angioblasts in somites and their directed migration toward the dorsal aorta in avian embryos,” Developmental Cell, vol. 14, no. 6, pp. 890–901, 2008. View at Publisher · View at Google Scholar · View at Scopus
  122. H. Schunkert, I. R. König, S. Kathiresan et al., “Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease,” Nature Genetics, vol. 43, no. 4, pp. 333–338, 2011. View at Publisher · View at Google Scholar · View at Scopus