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Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease

Author

Listed:
  • Yonatan R. Lewis-Israeli

    (Michigan State University
    Michigan State University)

  • Aaron H. Wasserman

    (Michigan State University
    Michigan State University)

  • Mitchell A. Gabalski

    (Michigan State University
    Michigan State University)

  • Brett D. Volmert

    (Michigan State University
    Michigan State University)

  • Yixuan Ming

    (Washington University in Saint Louis)

  • Kristen A. Ball

    (Michigan State University
    Michigan State University)

  • Weiyang Yang

    (Michigan State University
    Michigan State University)

  • Jinyun Zou

    (Washington University in Saint Louis)

  • Guangming Ni

    (Washington University in Saint Louis)

  • Natalia Pajares

    (Michigan State University)

  • Xanthippi Chatzistavrou

    (Michigan State University)

  • Wen Li

    (Michigan State University
    Michigan State University)

  • Chao Zhou

    (Washington University in Saint Louis)

  • Aitor Aguirre

    (Michigan State University
    Michigan State University)

Abstract

Congenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.

Suggested Citation

  • Yonatan R. Lewis-Israeli & Aaron H. Wasserman & Mitchell A. Gabalski & Brett D. Volmert & Yixuan Ming & Kristen A. Ball & Weiyang Yang & Jinyun Zou & Guangming Ni & Natalia Pajares & Xanthippi Chatzis, 2021. "Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25329-5
    DOI: 10.1038/s41467-021-25329-5
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    Cited by:

    1. Bas Loo & Simone A. Den & Nuno Araújo-Gomes & Vincent Jong & Rebecca R. Snabel & Maik Schot & José M. Rivera-Arbeláez & Gert Jan C. Veenstra & Robert Passier & Tom Kamperman & Jeroen Leijten, 2023. "Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Maksymilian Prondzynski & Paul Berkson & Michael A. Trembley & Yashasvi Tharani & Kevin Shani & Raul H. Bortolin & Mason E. Sweat & Joshua Mayourian & Dogacan Yucel & Albert M. Cordoves & Beatrice Gab, 2024. "Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Ian Fernandes & Shunsuke Funakoshi & Homaira Hamidzada & Slava Epelman & Gordon Keller, 2023. "Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Pengcheng Yang & Lihang Zhu & Shiya Wang & Jixing Gong & Jonathan Nimal Selvaraj & Lincai Ye & Hanxiao Chen & Yaoyao Zhang & Gongxin Wang & Wanjun Song & Zilong Li & Lin Cai & Hao Zhang & Donghui Zhan, 2024. "Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    5. Brett Volmert & Artem Kiselev & Aniwat Juhong & Fei Wang & Ashlin Riggs & Aleksandra Kostina & Colin O’Hern & Priyadharshni Muniyandi & Aaron Wasserman & Amanda Huang & Yonatan Lewis-Israeli & Vishal , 2023. "A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    6. Mariana A. Branco & Tiago P. Dias & Joaquim M. S. Cabral & Perpetua Pinto-do-Ó & Maria Margarida Diogo, 2022. "Human multilineage pro-epicardium/foregut organoids support the development of an epicardium/myocardium organoid," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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