Cardiomyocyte Differentiation

  • Dinender K. Singla
  • Shreeya Jayaraman
  • Jianhua Zhang
  • Timothy J. Kamp
Part of the Human Cell Culture book series (HUCC, volume 6)


Embryonic Stem Cell Human Embryonic Stem Cell hESC Line Cardiac Differentiation Cardiomyocyte Differentiation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Andrée, B., Duprez, D., Vorbusch, B., Arnold, H.H., and Brand, T. (1998) BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos. Mech. Dev., 70: 119–131.PubMedCrossRefGoogle Scholar
  2. Azpiazu, N. and Frasch, M. (1993) Tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. Genes Dev., 7: 1325–1340.PubMedCrossRefGoogle Scholar
  3. Barron, M., Gao, M., and Lough, J. (2000) Requirement for BMP and FGF signaling during cardiogenic induction in non-precardiac mesoderm is specific, transient, and cooperative. Dev. Dyn., 218: 383–393.PubMedCrossRefGoogle Scholar
  4. Behfar, A., Zingman, L.V., Hodgson, D.M., Rauzier, J.M., Kane, G.C., Terzic, A., and Puceat, M. (2002) Stem cell differentiation requires a paracrine pathway in the heart. FASEB J., 16: 1558–1566.PubMedCrossRefGoogle Scholar
  5. Bers, D.M. (2002) Cardiac excitation-contraction coupling. Nature, 415: 198–205.PubMedCrossRefGoogle Scholar
  6. Bodmer, R. (1993) The gene tinman is required for specification of the heart and visceral muscles in Drosophila. Development, 118: 719–729.PubMedGoogle Scholar
  7. Boheler, K.R., Czyz, J., Tweedie, D., Yang, H.T., Anisimov, S.V., and Wobus, A.M. (2002) Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ. Res., 91: 189–201.PubMedCrossRefGoogle Scholar
  8. Bruneau, B.G. (2002) Transcriptional regulation of vertebrate cardiac morphogenesis. Circ. Res., 90: 509–519.PubMedCrossRefGoogle Scholar
  9. Doetschman, T.C., Eistetter, H., Katz, M., Schmidt, W., and Kemler, R. (1985) The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morphol., 87: 27–45.PubMedGoogle Scholar
  10. Dolnikov, K., Shilkrut, M., Zeevi-Levin, N., Gerecht-Nir, S., Amit, M., Danon, A., Itskovitz-Eldor, J., and Binah, O. (2006) Functional properties of human embryonic stem cell-derived cardiomyocytes: intracellular Ca2+ handling and the role of sarcoplasmic reticulum in the contraction. Stem Cells, 24: 236–245.PubMedCrossRefGoogle Scholar
  11. Evans, M.J. and Kaufman, M.H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature, 292: 154–156.PubMedCrossRefGoogle Scholar
  12. He, J.Q., Ma, Y., Lee, Y., Thomson, J.A., and Kamp, T.J. (2003) Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ. Res., 93: 32–39.PubMedCrossRefGoogle Scholar
  13. Hidaka, K., Lee, J.K., Kim, H.S., Ihm, C.H., Iio, A., Ogawa, M., Nishikawa, S., Kodama, I., and Morisaki, T. (2003) Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells. FASEB J., 17: 740–742.PubMedGoogle Scholar
  14. Kehat, I., Gepstein, A., Spira, A., Itskovitz-Eldor, J., and Gepstein, L. (2002) High-resolution electrophysiological assessment of human embryonic stem cell-derived cardiomyocytes: a novel in vitro model for the study of conduction. Circ. Res., 91: 659–661.PubMedCrossRefGoogle Scholar
  15. Kehat, I., Kenyagin-Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J., and Gepstein, L. (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J. Clin. Invest., 108: 407–414.PubMedGoogle Scholar
  16. Klug, M.G., Soonpas, M.H., Koh, G.Y., and Field, L.J. (1996) Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J. Clin. Invest., 98: 216–224.PubMedCrossRefGoogle Scholar
  17. Kolossov, E., Fleischmann, B.K., Liu, Q., Bloch, W., Viatchenko-Karpinski, S., Manzke, O., Ji, G.J., Bohlen, H., Addicks, K., and Hescheler, J. (1998) Functional characteristics of ES cell-derived cardiac precursor cells identified by tissue-specific expression of the green fluorescent protein. J. Cell Biol., 143: 2045–2056.PubMedCrossRefGoogle Scholar
  18. Martin, G.R. (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA, 78: 7634–7638.PubMedCrossRefGoogle Scholar
  19. Marvin, M.J., Di Rocco, G., Gardiner, A., Bush, S.M., and Lassar, A.B. (2001) Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes Dev., 15: 316–327.PubMedCrossRefGoogle Scholar
  20. Metzger, J.M., Lin, W.I., and Samuelson, L.C. (1996) Vital staining of cardiac myocytes during embryonic stem cell cardiogenesis in vitro. Circ. Res., 78: 547–552.PubMedGoogle Scholar
  21. Meyer, N., Jaconi, M., Landopoulou, A., Fort, P., and Puceat, M. (2000) A fluorescent reporter gene as a marker for ventricular specification in ES-derived cardiac cells. FEBS Lett., 478: 151–158.PubMedCrossRefGoogle Scholar
  22. Muller, M., Fleischmann, B.K., Selbert, S., Ji, G.J., Endl, E., Middeler, G., Muller, O.J., Schlenke, P., Frese, S., Wobus, A.M., Hescheler, J., Katus, H.A., and Franz, W.M. (2000) Selection of ventricular-like cardiomyocytes from ES cells in vitro. FASEB J., 14: 2540–2548.PubMedCrossRefGoogle Scholar
  23. Mummery, C., Ward-van Oostwaard, D., Doevendans, P., Spijker, R., van den, B.S., Hassink, R., van der, H.M., Opthof, T., Pera, M., de la Riviere, A.B., Passier, R., and Tertoolen, L. (2003) Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation, 107: 2733–2740.PubMedCrossRefGoogle Scholar
  24. Olson, E.N. and Srivastava, D. (1996) Molecular pathways controlling heart development. Science, 272: 671–676.PubMedCrossRefGoogle Scholar
  25. Passier, R., Oostwaard, D.W., Snapper, J., Kloots, J., Hassink, R.J., Kuijk, E., Roelen, B., de la Riviere, A.B., and Mummery, C. (2005) Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Stem Cells, 23: 772–780.PubMedCrossRefGoogle Scholar
  26. Pegg, W. and Michalak, M. (1987) Differentiation of sarcoplasmic reticulum during cardiac myogenesis. Am. J. Physiol., 252: H22–H31.PubMedGoogle Scholar
  27. Rudy-Reil, D. and Lough, J. (2004) Avian precardiac endoderm/mesoderm induces cardiac myocyte differentiation in murine embryonic stem cells. Circ. Res., 94: e107–e116.PubMedCrossRefGoogle Scholar
  28. Satin, J., Kehat, I., Caspi, O., Huber, I., Arbel, G., Itzhaki, I., Magyar, J., Schroder, E.A., Perlman, I., and Gepstein, L. (2004) Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes. J. Physiol., 559: 479–496.PubMedCrossRefGoogle Scholar
  29. Schneider, V.A. and Mercola, M. (2001) Wnt antagonism initiates cardiogenesis in Xenopus laevis. Genes Dev., 15: 304–315.PubMedCrossRefGoogle Scholar
  30. Schram, G., Pourrier, M., Melnyk, P., and Nattel, S. (2002) Differential distribution of cardiac ion channel expression as a basis for regional specialization in electrical function. Circ. Res., 90: 939–950.PubMedCrossRefGoogle Scholar
  31. Schroeder, M., Niebruegge, S., Werner, A., Willbold, E., Burg, M., Ruediger, M., Field, L.J., Lehmann, J., and Zweigerdt, R. (2005) Differentiation and lineage selection of mouse embryonic stem cells in a stirred bench scale bioreactor with automated process control. Biotechnol. Bioeng., 92: 920–933.PubMedCrossRefGoogle Scholar
  32. Schultheiss, T.M., Burch, J.B., and Lassar, A.B. (1997) A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev., 11: 451–462.PubMedCrossRefGoogle Scholar
  33. Segev, H., Kenyagin-Karsenti, D., Fishman, B., Gerecht-Nir, S., Ziskind, A., Amit, M., Coleman, R., and Itskovitz-Eldor, J. (2005) Molecular analysis of cardiomyocytes derived from human embryonic stem cells. Dev. Growth Differ., 47: 295–306.PubMedCrossRefGoogle Scholar
  34. Snir, M., Kehat, I., Gepstein, A., Coleman, R., Itskovitz-Eldor, J., Livne, E., and Gepstein, L. (2003) Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes. Am. J. Physiol. Heart. Circ. Physiol., 285: H2355–H2363.PubMedGoogle Scholar
  35. Takahashi, T., Lord, B., Schulze, P.C., Fryer, R.M., Sarang, S.S., Gullans, S.R., and Lee, R.T. (2003) Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Circulation, 107: 1912–1916.PubMedCrossRefGoogle Scholar
  36. Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., and Jones, J.M. (1998) Embryonic stem cell lines derived from human blastocysts. Science, 282: 1145–1147.PubMedCrossRefGoogle Scholar
  37. Winnier, G., Blessing, M., Labosky, P.A., and Hogan, B.L. (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev., 9: 2105–2116.PubMedCrossRefGoogle Scholar
  38. Wu, X., Ding, S., Ding, Q., Gray, N.S., and Schultz, P.G. (2004) Small molecules that induce cardiomyogenesis in embryonic stem cells. J. Am. Chem. Soc., 126: 1590–1591.PubMedCrossRefGoogle Scholar
  39. Xu, C., Police, S., Rao, N., and Carpenter, M.K. (2002a) Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ. Res., 91: 501–508.PubMedCrossRefGoogle Scholar
  40. Xu, R.H., Chen, X., Li, D.S., Li, R., Addicks, G.C., Glennon, C., Zwaka, T.P., and Thomson, J.A. (2002b) BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat. Biotechnol., 20: 1261–1264.PubMedCrossRefGoogle Scholar
  41. Xue, T., Cho, H.C., Akar, F.G., Tsang, S.Y., Jones, S.P., Marban, E., Tomaselli, G.F., and Li, R.A. (2005) Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation, 111: 11–20.PubMedCrossRefGoogle Scholar
  42. Yuasa, S., Itabashi, Y., Koshimizu, U., Tanaka, T., Sugimura, K., Kinoshita, M., Hattori, F., Fukami, S., Shimazaki, T., Ogawa, S., Okano, H., and Fukuda, K. (2005) Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells. Nat. Biotechnol., 23: 607–611.PubMedCrossRefGoogle Scholar
  43. Zaffran, S. and Frasch, M. (2002) Early signals in cardiac development. Circ. Res., 91: 457–469.PubMedCrossRefGoogle Scholar
  44. Zhang, H. and Bradley, A. (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development, 122: 2977–2986.PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Dinender K. Singla
    • 1
  • Shreeya Jayaraman
    • 2
  • Jianhua Zhang
    • 3
  • Timothy J. Kamp
    • 4
  1. 1.Cardiovascular Research InstituteUniversity of VermontColchesterUSA
  2. 2.Division of Cardiovascular MedicineUniversity of WisconsinMadisonUSA
  3. 3.Division of Cardiovascular MedicineUniversity of WisconsinMadisonUSA
  4. 4.Division of Cardiovascular MedicineUniversity of WisconsinMadisonUSA

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