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In vitro generation of functional murine heart organoids via FGF4 and extracellular matrix

Author

Listed:
  • Jiyoung Lee

    (Tokyo Medical and Dental University (TMDU))

  • Akito Sutani

    (Tokyo Medical and Dental University (TMDU)
    Tokyo Medical and Dental University (TMDU))

  • Rin Kaneko

    (Tokyo Medical and Dental University (TMDU))

  • Jun Takeuchi

    (Tokyo Medical and Dental University (TMDU))

  • Tetsuo Sasano

    (Tokyo Medical and Dental University (TMDU))

  • Takashi Kohda

    (Tokyo Medical and Dental University (TMDU)
    University of Yamanashi)

  • Kensuke Ihara

    (Tokyo Medical and Dental University (TMDU))

  • Kentaro Takahashi

    (Tokyo Medical and Dental University (TMDU))

  • Masahiro Yamazoe

    (Tokyo Medical and Dental University (TMDU))

  • Tomohiro Morio

    (Tokyo Medical and Dental University (TMDU))

  • Tetsushi Furukawa

    (Tokyo Medical and Dental University (TMDU))

  • Fumitoshi Ishino

    (Tokyo Medical and Dental University (TMDU))

Abstract

Our understanding of the spatiotemporal regulation of cardiogenesis is hindered by the difficulties in modeling this complex organ currently by in vitro models. Here we develop a method to generate heart organoids from mouse embryonic stem cell-derived embryoid bodies. Consecutive morphological changes proceed in a self-organizing manner in the presence of the laminin-entactin (LN/ET) complex and fibroblast growth factor 4 (FGF4), and the resulting in vitro heart organoid possesses atrium- and ventricle-like parts containing cardiac muscle, conducting tissues, smooth muscle and endothelial cells that exhibited myocardial contraction and action potentials. The heart organoids exhibit ultrastructural, histochemical and gene expression characteristics of considerable similarity to those of developmental hearts in vivo. Our results demonstrate that this method not only provides a biomimetic model of the developing heart-like structure with simplified differentiation protocol, but also represents a promising research tool with a broad range of applications, including drug testing.

Suggested Citation

  • Jiyoung Lee & Akito Sutani & Rin Kaneko & Jun Takeuchi & Tetsuo Sasano & Takashi Kohda & Kensuke Ihara & Kentaro Takahashi & Masahiro Yamazoe & Tomohiro Morio & Tetsushi Furukawa & Fumitoshi Ishino, 2020. "In vitro generation of functional murine heart organoids via FGF4 and extracellular matrix," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18031-5
    DOI: 10.1038/s41467-020-18031-5
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