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A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization

Author

Listed:
  • Brett Volmert

    (Michigan State University
    Michigan State University)

  • Artem Kiselev

    (Michigan State University
    Michigan State University
    Michigan State University)

  • Aniwat Juhong

    (Michigan State University
    Michigan State University)

  • Fei Wang

    (Washington University in Saint Louis)

  • Ashlin Riggs

    (Michigan State University
    Michigan State University)

  • Aleksandra Kostina

    (Michigan State University
    Michigan State University)

  • Colin O’Hern

    (Michigan State University
    Michigan State University)

  • Priyadharshni Muniyandi

    (Michigan State University
    Michigan State University)

  • Aaron Wasserman

    (Michigan State University
    Michigan State University)

  • Amanda Huang

    (Michigan State University
    Michigan State University)

  • Yonatan Lewis-Israeli

    (Michigan State University
    Michigan State University)

  • Vishal Panda

    (Michigan State University
    Michigan State University)

  • Sudin Bhattacharya

    (Michigan State University
    Michigan State University)

  • Adam Lauver

    (Michigan State University)

  • Sangbum Park

    (Michigan State University
    Michigan State University
    Michigan State University)

  • Zhen Qiu

    (Michigan State University
    Michigan State University)

  • Chao Zhou

    (Washington University in Saint Louis)

  • Aitor Aguirre

    (Michigan State University
    Michigan State University)

Abstract

Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g., addition of metabolic and hormonal factors) would lead to higher physiological and anatomical relevance. We find that heart organoids produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally and morphologically to age-matched human embryonic hearts. We also show that they recapitulate several aspects of cardiac development, including large atrial and ventricular chambers, proepicardial organ formation, and retinoic acid-mediated anterior-posterior patterning, mimicking the developmental processes found in the post-heart tube stage primitive heart. Moreover, we provide proof-of-concept demonstration of the value of this system for disease modeling by exploring the effects of ondansetron, a drug administered to pregnant women and associated with congenital heart defects. These findings constitute a significant technical advance for synthetic heart development and provide a powerful tool for cardiac disease modeling.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43999-1
    DOI: 10.1038/s41467-023-43999-1
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    References listed on IDEAS

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    2. 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.
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