1932

Abstract

Regeneration or replacement of lost cardiomyocytes within the heart has the potential to revolutionize cardiovascular medicine. Numerous methodologies have been used to achieve this aim, including the engraftment of bone marrow- and heart-derived cells as well as the identification of modulators of adult cardiomyocyte proliferation. Recently, the conversion of human somatic cells into induced pluripotent stem cells and induced cardiomyocyte-like cells has transformed potential approaches toward this goal, and the engraftment of cardiac progenitors derived from human embryonic stem cells into patients is now feasible. Here we review recent advances in our understanding of the genetic and epigenetic control of human cardiogenesis, cardiac differentiation, and the induced reprogramming of somatic cells to cardiomyocytes. We also cover genetic programs for inducing the proliferation of endogenous cardiomyocytes and discuss the genetic state of cells used in cardiac regenerative medicine.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-112414-054911
2015-11-23
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/genet/49/1/annurev-genet-112414-054911.html?itemId=/content/journals/10.1146/annurev-genet-112414-054911&mimeType=html&fmt=ahah

Literature Cited

  1. Ang SL, Constam DB. 1.  2004. A gene network establishing polarity in the early mouse embryo. Semin. Cell Dev. Biol. 15:555–61 [Google Scholar]
  2. Armstrong L, Hughes O, Yung S, Hyslop L, Stewart R. 2.  et al. 2006. The role of PI3K/AKT, MAPK/ERK and NFκβ signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis. Hum. Mol. Genet. 15:1894–913 [Google Scholar]
  3. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F. 3.  et al. 2003. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–76 [Google Scholar]
  4. Bendall SC, Stewart MH, Menendez P, George D, Vijayaragavan K. 4.  et al. 2007. IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature 448:1015–21 [Google Scholar]
  5. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F. 5.  et al. 2009. Evidence for cardiomyocyte renewal in humans. Science 324:98–102 [Google Scholar]
  6. Bersell K, Arab S, Haring B, Kuhn B. 6.  2009. Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 138:257–70 [Google Scholar]
  7. Bicknell KA, Coxon CH, Brooks G. 7.  2004. Forced expression of the cyclin B1-CDC2 complex induces proliferation in adult rat cardiomyocytes. Biochem. J. 382:411–16 [Google Scholar]
  8. Bizy A, Guerrero-Serna G, Hu B, Ponce-Balbuena D, Willis BC. 8.  et al. 2013. Myosin light chain 2–based selection of human iPSC-derived early ventricular cardiac myocytes. Stem Cell Res. 11:1335–47 [Google Scholar]
  9. Blin G, Nury D, Stefanovic S, Neri T, Guillevic O. 9.  et al. 2010. A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. J. Clin. Investig. 120:1125–39 [Google Scholar]
  10. Bolli R, Chugh AR, D'Amario D, Loughran JH, Stoddard MF. 10.  et al. 2011. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378:1847–57 [Google Scholar]
  11. Bondue A, Lapouge G, Paulissen C, Semeraro C, Iacovino M. 11.  et al. 2008. Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. Cell Stem Cell 3:69–84 [Google Scholar]
  12. Bondue A, Tannler S, Chiapparo G, Chabab S, Ramialison M. 12.  et al. 2011. Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation. J. Cell Biol. 192:751–65 [Google Scholar]
  13. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS. 13.  et al. 2005. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–56 [Google Scholar]
  14. Buckingham M, Meilhac S, Zaffran S. 14.  2005. Building the mammalian heart from two sources of myocardial cells. Nat. Rev. Genet. 6:826–35 [Google Scholar]
  15. Burridge PW, Anderson D, Priddle H, Barbadillo Munoz MD, Chamberlain S. 15.  et al. 2007. Improved human embryonic stem cell embryoid body homogeneity and cardiomyocyte differentiation from a novel V-96 plate aggregation system highlights interline variability. Stem Cells 25:929–38 [Google Scholar]
  16. Burridge PW, Keller G, Gold JD, Wu JC. 16.  2012. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10:16–28 [Google Scholar]
  17. Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM. 17.  et al. 2014. Chemically defined generation of human cardiomyocytes. Nat. Methods 11:855–60 [Google Scholar]
  18. Burridge PW, Thompson S, Millrod MA, Weinberg S, Yuan X. 18.  et al. 2011. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability. PLOS ONE 6:e18293 [Google Scholar]
  19. Cao N, Liang H, Huang J, Wang J, Chen Y. 19.  et al. 2013. Highly efficient induction and long-term maintenance of multipotent cardiovascular progenitors from human pluripotent stem cells under defined conditions. Cell Res. 23:1119–32 [Google Scholar]
  20. Chamberlain AA, Lin M, Lister RL, Maslov AA, Wang Y. 20.  et al. 2014. DNA methylation is developmentally regulated for genes essential for cardiogenesis. J. Am. Heart Assoc. 3:e000976 [Google Scholar]
  21. Chambers I, Silva J, Colby D, Nichols J, Nijmeijer B. 21.  et al. 2007. Nanog safeguards pluripotency and mediates germline development. Nature 450:1230–34 [Google Scholar]
  22. Chan SS, Shi X, Toyama A, Arpke RW, Dandapat A. 22.  et al. 2013. Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner. Cell Stem Cell 12:587–601 [Google Scholar]
  23. Chen J, Huang ZP, Seok HY, Ding J, Kataoka M. 23.  et al. 2013. mir-17–92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ. Res. 112:1557–66 [Google Scholar]
  24. Chen JF, Murchison EP, Tang R, Callis TE, Tatsuguchi M. 24.  et al. 2008. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. PNAS 105:2111–16 [Google Scholar]
  25. Chen L, Wang Y, Pan Y, Zhang L, Shen C. 25.  et al. 2013. Cardiac progenitor–derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem. Biophys. Res. Commun. 431:566–71 [Google Scholar]
  26. Cheng HL, Mostoslavsky R, Saito S, Manis JP, Gu Y. 26.  et al. 2003. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. PNAS 100:10794–99 [Google Scholar]
  27. Chong JJ, Yang X, Don CW, Minami E, Liu YW. 27.  et al. 2014. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510:273–77 [Google Scholar]
  28. Chuva de Sousa Lopes SM, Hassink RJ, Feijen A, van Rooijen MA, Doevendans PA. 28.  et al. 2006. Patterning the heart, a template for human cardiomyocyte development. Dev. Dyn. 235:1994–2002 [Google Scholar]
  29. Dalton S. 29.  2013. Signaling networks in human pluripotent stem cells. Curr. Opin. Cell Biol. 25:241–46 [Google Scholar]
  30. David R, Brenner C, Stieber J, Schwarz F, Brunner S. 30.  et al. 2008. MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling. Nat. Cell Biol. 10:338–45 [Google Scholar]
  31. Davidson KC, Adams AM, Goodson JM, McDonald CE, Potter JC. 31.  et al. 2012. Wnt/β-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4. PNAS 109:4485–90 [Google Scholar]
  32. Davis RL, Weintraub H, Lassar AB. 32.  1987. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51:987–1000 [Google Scholar]
  33. Devalla HD, Schwach V, Ford JW, Milnes JT, El-Haou S. 33.  et al. 2015. Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology. EMBO Mol. Med. 7:394–410 [Google Scholar]
  34. Devine WP, Wythe JD, George M, Koshiba-Takeuchi K, Bruneau BG. 34.  2014. Early patterning and specification of cardiac progenitors in gastrulating mesoderm. eLife 3:e03848 [Google Scholar]
  35. Dey D, Han L, Bauer M, Sanada F, Oikonomopoulos A. 35.  et al. 2013. Dissecting the molecular relationship among various cardiogenic progenitor cells. Circ. Res. 112:1253–62 [Google Scholar]
  36. Ding Q, Lee YK, Schaefer EA, Peters DT, Veres A. 36.  et al. 2013. A TALEN genome-editing system for generating human stem cell–based disease models. Cell Stem Cell 12:238–51 [Google Scholar]
  37. Dodou E, Verzi MP, Anderson JP, Xu SM, Black BL. 37.  2004. Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Development 131:3931–42 [Google Scholar]
  38. Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K. 38.  et al. 2011. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat. Cell Biol. 13:215–22 [Google Scholar]
  39. Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A. 39.  et al. 2013. Adult c-kitpos cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell 154:827–42 [Google Scholar]
  40. Engel FB, Schebesta M, Duong MT, Lu G, Ren S. 40.  et al. 2005. p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev. 19:1175–87 [Google Scholar]
  41. Evans MJ, Kaufman MH. 41.  1981. Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–56 [Google Scholar]
  42. Filipczyk A, Gkatzis K, Fu J, Hoppe PS, Lickert H. 42.  et al. 2013. Biallelic expression of Nanog protein in mouse embryonic stem cells. Cell Stem Cell 13:12–13 [Google Scholar]
  43. Foley AC, Mercola M. 43.  2005. Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex. Genes Dev. 19:387–96 [Google Scholar]
  44. Fu JD, Stone NR, Liu L, Spencer CI, Qian L. 44.  et al. 2013. Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Rep. 1:235–47 [Google Scholar]
  45. Gonzalez R, Lee JW, Schultz PG. 45.  2011. Stepwise chemically induced cardiomyocyte specification of human embryonic stem cells. Angew. Chem. Int. Ed. 50:11181–85 [Google Scholar]
  46. Gottlieb PD, Pierce SA, Sims RJ, Yamagishi H, Weihe EK. 46.  et al. 2002. Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nat. Genet. 31:25–32 [Google Scholar]
  47. Grote P, Wittler L, Hendrix D, Koch F, Wahrisch S. 47.  et al. 2013. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev. Cell 24:206–14 [Google Scholar]
  48. Hang CT, Yang J, Han P, Cheng HL, Shang C. 48.  et al. 2010. Chromatin regulation by Brg1 underlies heart muscle development and disease. Nature 466:62–67 [Google Scholar]
  49. Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E. 49.  et al. 2011. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 332:458–61 [Google Scholar]
  50. Herrmann F, Gross A, Zhou D, Kestler HA, Kuhl M. 50.  2012. A Boolean model of the cardiac gene regulatory network determining first and second heart field identity. PLOS ONE 7:e46798 [Google Scholar]
  51. Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y. 51.  et al. 2001. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat. Genet. 28:276–80 [Google Scholar]
  52. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y. 52.  et al. 2010. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142:375–86 [Google Scholar]
  53. Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T. 53.  et al. 2012. Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. Circ. Res. 111:1147–56 [Google Scholar]
  54. James D, Levine AJ, Besser D, Hemmati-Brivanlou A. 54.  2005. TGFβ/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132:1273–82 [Google Scholar]
  55. Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA. 55.  et al. 2012. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ. Res. 110:1465–73 [Google Scholar]
  56. Josowitz R, Lu J, Falce C, D'Souza SL, Wu M. 56.  et al. 2014. Identification and purification of human induced pluripotent stem cell–derived atrial-like cardiomyocytes based on sarcolipin expression. PLOS ONE 9:e101316 [Google Scholar]
  57. Kaiser J. 57.  2004. Gene therapy. Side effects sideline hemophilia trial. Science 304:1423–25 [Google Scholar]
  58. Kalmar T, Lim C, Hayward P, Munoz-Descalzo S, Nichols J. 58.  et al. 2009. Regulated fluctuations in Nanog expression mediate cell fate decisions in embryonic stem cells. PLOS Biol. 7:e1000149 [Google Scholar]
  59. Karantalis V, DiFede DL, Gerstenblith G, Pham S, Symes J. 59.  et al. 2014. Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: the Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial. Circ. Res. 114:1302–10 [Google Scholar]
  60. Karikkineth BC, Zimmermann WH. 60.  2013. Myocardial tissue engineering and heart muscle repair. Curr. Pharm. Biotechnol. 14:4–11 [Google Scholar]
  61. Kattman SJ, Witty AD, Gagliardi M, Dubois NC, Niapour M. 61.  et al. 2011. Stage-specific optimization of Activin/Nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8:228–40 [Google Scholar]
  62. Katz TC, Singh MK, Degenhardt K, Rivera-Feliciano J, Johnson RL. 62.  et al. 2012. Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells. Dev. Cell 22:639–50 [Google Scholar]
  63. Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M. 63.  et al. 2001. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J. Clin. Investig. 108:407–14 [Google Scholar]
  64. Kempf H, Olmer R, Kropp C, Ruckert M, Jara-Avaca M. 64.  et al. 2014. Controlling expansion and cardiomyogenic differentiation of human pluripotent stem cells in scalable suspension culture. Stem Cell Rep. 3:1132–46 [Google Scholar]
  65. Klattenhoff CA, Scheuermann JC, Surface LE, Bradley RK, Fields PA. 65.  et al. 2013. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 152:570–83 [Google Scholar]
  66. Knezevic I, Patel A, Sundaresan NR, Gupta MP, Solaro RJ. 66.  et al. 2012. A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth factor 1 receptor: implications in postnatal cardiac remodeling and cell survival. J. Biol. Chem. 287:12913–26 [Google Scholar]
  67. Kuhn B, del Monte F, Hajjar RJ, Chang YS, Lebeche D. 67.  et al. 2007. Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat. Med. 13:962–69 [Google Scholar]
  68. Kwon C, Arnold J, Hsiao EC, Taketo MM, Conklin BR, Srivastava D. 68.  2007. Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors. PNAS 104:10894–99 [Google Scholar]
  69. Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA. 69.  et al. 2007. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat. Biotechnol. 25:1015–24 [Google Scholar]
  70. Lescroart F, Chabab S, Lin X, Rulands S, Paulissen C. 70.  et al. 2014. Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development. Nat. Cell Biol. 16:829–40 [Google Scholar]
  71. Li J, Gao E, Vite A, Yi R, Gomez L. 71.  et al. 2015. α-Catenins control cardiomyocyte proliferation by regulating Yap activity. Circ. Res. 116:70–79 [Google Scholar]
  72. Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB. 72.  et al. 2012. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. PNAS 109:E1848–57 [Google Scholar]
  73. Lickert H, Takeuchi JK, Von Both I, Walls JR, McAuliffe F. 73.  et al. 2004. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432:107–12 [Google Scholar]
  74. Lieu DK, Fu JD, Chiamvimonvat N, Tung KC, McNerney GP. 74.  et al. 2013. Mechanism-based facilitated maturation of human pluripotent stem cell–derived cardiomyocytes. Circ. Arrhythm. Electrophysiol. 6:191–201 [Google Scholar]
  75. Lin Z, Zhou P, von Gise A, Gu F, Ma Q. 75.  et al. 2015. Pi3kcb links Hippo-YAP and PI3K-AKT signaling pathways to promote cardiomyocyte proliferation and survival. Circ. Res. 116:35–45 [Google Scholar]
  76. Lindsley RC, Gill JG, Murphy TL, Langer EM, Cai M. 76.  et al. 2008. Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs. Cell Stem Cell 3:55–68 [Google Scholar]
  77. Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA. 77.  et al. 2008. MicroRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 22:3242–54 [Google Scholar]
  78. Lundy SD, Zhu WZ, Regnier M, Laflamme MA. 78.  2013. Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cells Dev. 22:1991–2002 [Google Scholar]
  79. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE. 79.  et al. 2012. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379:895–904 [Google Scholar]
  80. Matkovich SJ, Edwards JR, Grossenheider TC, de Guzman Strong C, Dorn GW II. 80.  2014. Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs. PNAS 111:12264–69 [Google Scholar]
  81. McDevitt TC, Laflamme MA, Murry CE. 81.  2005. Proliferation of cardiomyocytes derived from human embryonic stem cells is mediated via the IGF/PI 3-kinase/Akt signaling pathway. J. Mol. Cell. Cardiol. 39:865–73 [Google Scholar]
  82. Menasché P, Vanneaux V, Fabreguettes JR, Bel A, Tosca L. 82.  et al. 2015. Towards a clinical use of human embryonic stem cell–derived cardiac progenitors: a translational experience. Eur. Heart J. 36:743–50 [Google Scholar]
  83. Mendjan S, Mascetti VL, Ortmann D, Ortiz M, Karjosukarso DW. 83.  et al. 2014. NANOG and CDX2 pattern distinct subtypes of human mesoderm during exit from pluripotency. Cell Stem Cell 15:310–25 [Google Scholar]
  84. Montgomery RL, Davis CA, Potthoff MJ, Haberland M, Fielitz J. 84.  et al. 2007. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev. 21:1790–802 [Google Scholar]
  85. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A. 85.  et al. 2006. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127:1151–65 [Google Scholar]
  86. Mysliwiec MR, Carlson CD, Tietjen J, Hung H, Ansari AZ, Lee Y. 86.  2012. Jarid2 (Jumonji, AT rich interactive domain 2) regulates NOTCH1 expression via histone modification in the developing heart. J. Biol. Chem. 287:1235–41 [Google Scholar]
  87. Navarro P, Festuccia N, Colby D, Gagliardi A, Mullin NP. 87.  et al. 2012. OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cells. EMBO J. 31:4547–62 [Google Scholar]
  88. Nimura K, Ura K, Shiratori H, Ikawa M, Okabe M. 88.  et al. 2009. A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature 460:287–91 [Google Scholar]
  89. Nowbar AN, Mielewczik M, Karavassilis M, Dehbi HM, Shun-Shin MJ. 89.  et al. 2014. Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis. BMJ 348:g2688 [Google Scholar]
  90. Ong SG, Lee WH, Huang M, Dey D, Kodo K. 90.  et al. 2014. Cross talk of combined gene and cell therapy in ischemic heart disease: role of exosomal microRNA transfer. Circulation 130:S60–69 [Google Scholar]
  91. Oyama T, Nagai T, Wada H, Naito AT, Matsuura K. 91.  et al. 2007. Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo. J. Cell Biol. 176:329–41 [Google Scholar]
  92. Paige SL, Osugi T, Afanasiev OK, Pabon L, Reinecke H, Murry CE. 92.  2010. Endogenous Wnt/β-catenin signaling is required for cardiac differentiation in human embryonic stem cells. PLOS ONE 5:e11134 [Google Scholar]
  93. Park EJ, Ogden LA, Talbot A, Evans S, Cai CL. 93.  et al. 2006. Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling. Development 133:2419–33 [Google Scholar]
  94. Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA. 94.  et al. 2011. Transient regenerative potential of the neonatal mouse heart. Science 331:1078–80 [Google Scholar]
  95. Porrello ER, Mahmoud AI, Simpson E, Johnson BA, Grinsfelder D. 95.  et al. 2013. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. PNAS 110:187–92 [Google Scholar]
  96. Poss KD, Wilson LG, Keating MT. 96.  2002. Heart regeneration in zebrafish. Science 298:2188–90 [Google Scholar]
  97. Prall OW, Menon MK, Solloway MJ, Watanabe Y, Zaffran S. 97.  et al. 2007. An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell 128:947–59 [Google Scholar]
  98. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V. 98.  et al. 2012. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485:593–98 [Google Scholar]
  99. Qian L, Wythe JD, Liu J, Cartry J, Vogler G. 99.  et al. 2011. Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species. J. Cell Biol. 193:1181–96 [Google Scholar]
  100. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. 100.  2013. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8:2281–308 [Google Scholar]
  101. Rana P, Anson B, Engle S, Will Y. 101.  2012. Characterization of human induced pluripotent stem cell derived cardiomyocytes: bioenergetics and utilization in safety screening. Toxicol. Sci. 130:117–31 [Google Scholar]
  102. Rao PK, Toyama Y, Chiang HR, Gupta S, Bauer M. 102.  et al. 2009. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ. Res. 105:585–94 [Google Scholar]
  103. Robertson EJ, Norris DP, Brennan J, Bikoff EK. 103.  2003. Control of early anterior-posterior patterning in the mouse embryo by TGF-β signalling. Philos. Trans. R. Soc. B 358:1351–57 [Google Scholar]
  104. Sandstedt J, Jonsson M, Kajic K, Sandstedt M, Lindahl A. 104.  et al. 2012. Left atrium of the human adult heart contains a population of side population cells. Basic Res. Cardiol. 107:255 [Google Scholar]
  105. Shiba Y, Fernandes S, Zhu WZ, Filice D, Muskheli V. 105.  et al. 2012. Human ES-cell–derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature 489:322–25 [Google Scholar]
  106. Shimoji K, Yuasa S, Onizuka T, Hattori F, Tanaka T. 106.  et al. 2010. G-CSF promotes the proliferation of developing cardiomyocytes in vivo and in derivation from ESCs and iPSCs. Cell Stem Cell 6:227–37 [Google Scholar]
  107. Shirai M, Osugi T, Koga H, Kaji Y, Takimoto E. 107.  et al. 2002. The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis. J. Clin. Investig. 110:177–84 [Google Scholar]
  108. Sluijter JP, van Mil A, van Vliet P, Metz CH, Liu J. 108.  et al. 2010. MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler. Thromb. Vasc. Biol. 30:859–68 [Google Scholar]
  109. Smith RR, Barile L, Cho HC, Leppo MK, Hare JM. 109.  et al. 2007. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation 115:896–908 [Google Scholar]
  110. Solloway MJ, Harvey RP. 110.  2003. Molecular pathways in myocardial development: a stem cell perspective. Cardiovasc. Res. 58:264–77 [Google Scholar]
  111. Song K, Nam YJ, Luo X, Qi X, Tan W. 111.  et al. 2012. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 485:599–604 [Google Scholar]
  112. Spater D, Abramczuk MK, Buac K, Zangi L, Stachel MW. 112.  et al. 2013. A HCN4 +cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat. Cell Biol. 15:1098–106 [Google Scholar]
  113. Takahashi K, Yamanaka S. 113.  2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–76 [Google Scholar]
  114. Takaya T, Kawamura T, Morimoto T, Ono K, Kita T. 114.  et al. 2008. Identification of p300-targeted acetylated residues in GATA4 during hypertrophic responses in cardiac myocytes. J. Biol. Chem. 283:9828–35 [Google Scholar]
  115. Takeuchi JK, Bruneau BG. 115.  2009. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459:708–11 [Google Scholar]
  116. Takeuchi JK, Lou X, Alexander JM, Sugizaki H, Delgado-Olguin P. 116.  et al. 2011. Chromatin remodelling complex dosage modulates transcription factor function in heart development. Nat. Commun. 2:187 [Google Scholar]
  117. Tam PP, Loebel DA. 117.  2007. Gene function in mouse embryogenesis: get set for gastrulation. Nat. Rev. Genet. 8:368–81 [Google Scholar]
  118. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ. 118.  et al. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282:1145–47 [Google Scholar]
  119. Thum T, Gross C, Fiedler J, Fischer T, Kissler S. 119.  et al. 2008. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456:980–84 [Google Scholar]
  120. Tran TH, Wang X, Browne C, Zhang Y, Schinke M. 120.  et al. 2009. Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells. Stem Cells 27:1869–78 [Google Scholar]
  121. Tseng AS, Engel FB, Keating MT. 121.  2006. The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes. Chem. Biol. 13:957–63 [Google Scholar]
  122. Uchida S, De Gaspari P, Kostin S, Jenniches K, Kilic A. 122.  et al. 2013. Sca1-derived cells are a source of myocardial renewal in the murine adult heart. Stem Cell Rep. 1:397–410 [Google Scholar]
  123. Uosaki H, Magadum A, Seo K, Fukushima H, Takeuchi A. 123.  et al. 2013. Identification of chemicals inducing cardiomyocyte proliferation in developmental stage–specific manner with pluripotent stem cells. Circ. Cardiovasc. Genet. 6:624–33 [Google Scholar]
  124. van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J. 124.  et al. 2014. c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature 509:337–41 [Google Scholar]
  125. van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X. 125.  et al. 2009. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev. Cell 17:662–73 [Google Scholar]
  126. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH. 126.  et al. 2008. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. PNAS 105:13027–32 [Google Scholar]
  127. van Vliet P, Roccio M, Smits AM, van Oorschot AA, Metz CH. 127.  et al. 2008. Progenitor cells isolated from the human heart: a potential cell source for regenerative therapy. Neth. Heart J. 16:163–69 [Google Scholar]
  128. Voss AK, Vanyai HK, Collin C, Dixon MP, McLennan TJ. 128.  et al. 2012. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev. Cell 23:652–63 [Google Scholar]
  129. Wang Z, Oron E, Nelson B, Razis S, Ivanova N. 129.  2012. Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells. Cell Stem Cell 10:440–54 [Google Scholar]
  130. Wang Z, Zhai W, Richardson JA, Olson EN, Meneses JJ. 130.  et al. 2004. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation. Genes Dev. 18:3106–16 [Google Scholar]
  131. Watanabe Y, Zaffran S, Kuroiwa A, Higuchi H, Ogura T. 131.  et al. 2012. Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium. PNAS 109:18273–80 [Google Scholar]
  132. Wessels A, Sedmera D. 132.  2003. Developmental anatomy of the heart: a tale of mice and man. Physiol. Genomics 15:165–76 [Google Scholar]
  133. Willems E, Spiering S, Davidovics H, Lanier M, Xia Z. 133.  et al. 2011. Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell–derived mesoderm. Circ. Res. 109:360–64 [Google Scholar]
  134. Wilson KD, Hu S, Venkatasubrahmanyam S, Fu JD, Sun N. 134.  et al. 2010. Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circ. Cardiovasc. Genet. 3:426–35 [Google Scholar]
  135. Wystub K, Besser J, Bachmann A, Boettger T, Braun T. 135.  2013. miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development. PLOS Genet. 9:e1003793 [Google Scholar]
  136. Yang B, Lin H, Xiao J, Lu Y, Luo X. 136.  et al. 2007. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat. Med. 13:486–91 [Google Scholar]
  137. Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ. 137.  et al. 2008. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453:524–28 [Google Scholar]
  138. Yang L, Xiao X. 138.  2013. Creation of a cardiotropic adeno-associated virus: the story of viral directed evolution. Virol. J. 10:50 [Google Scholar]
  139. Yang X, Pabon L, Murry CE. 139.  2014. Engineering adolescence: maturation of human pluripotent stem cell–derived cardiomyocytes. Circ. Res. 114:511–23 [Google Scholar]
  140. Yang X, Rodriguez M, Pabon L, Fischer KA, Reinecke H. 140.  et al. 2014. Tri-iodo-L-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. J. Mol. Cell. Cardiol. 72:296–304 [Google Scholar]
  141. Yao TP, Oh SP, Fuchs M, Zhou ND, Ch'ng LE. 141.  et al. 1998. Gene dosage–dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93:361–72 [Google Scholar]
  142. Ye L, Chang YH, Xiong Q, Zhang P, Zhang L. 142.  et al. 2014. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell–derived cardiovascular cells. Cell Stem Cell 15:750–61 [Google Scholar]
  143. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL. 143.  et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–20 [Google Scholar]
  144. Zeineddine D, Papadimou E, Chebli K, Gineste M, Liu J. 144.  et al. 2006. Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a cardiac lineage and early heart development. Dev. Cell 11:535–46 [Google Scholar]
  145. Zhang Q, Jiang J, Han P, Yuan Q, Zhang J. 145.  et al. 2011. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals. Cell Res. 21:579–87 [Google Scholar]
  146. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M. 146.  et al. 2007. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129:303–17 [Google Scholar]
  147. Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I. 147.  et al. 2008. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454:109–13 [Google Scholar]
  148. Zhu WZ, Xie Y, Moyes KW, Gold JD, Askari B, Laflamme MA. 148.  2010. Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells.. Circ. Res. 107:776–86 [Google Scholar]
/content/journals/10.1146/annurev-genet-112414-054911
Loading
/content/journals/10.1146/annurev-genet-112414-054911
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error