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Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools

Author

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  • Dorota Zawada

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Jessica Kornherr

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Anna B. Meier

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Gianluca Santamaria

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health
    University “Magna Graecia”)

  • Tatjana Dorn

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Monika Nowak-Imialek

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Daniel Ortmann

    (University of Cambridge
    University of Cambridge)

  • Fangfang Zhang

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Mark Lachmann

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance)

  • Martina Dreßen

    (Institute Insure - Technical University of Munich, School of Medicine and Health)

  • Mariaestela Ortiz

    (University of Cambridge)

  • Victoria L. Mascetti

    (Bristol Heart Institute, Bristol Medical School, Translational Health Sciences)

  • Stephen C. Harmer

    (University of Bristol)

  • Muriel Nobles

    (Queen Mary University of London)

  • Andrew Tinker

    (Queen Mary University of London)

  • Maria Teresa Angelis

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    University “Magna Graecia”)

  • Roger A. Pedersen

    (Stanford University)

  • Phillip Grote

    (Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy
    Goethe University)

  • Karl-Ludwig Laugwitz

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance)

  • Alessandra Moretti

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health
    Yale University School of Medicine)

  • Alexander Goedel

    (Technical University of Munich, School of Medicine and Health
    Karolinska Institute)

Abstract

Cardiogenesis relies on the precise spatiotemporal coordination of multiple progenitor populations. Understanding the specification and differentiation of these distinct progenitor pools during human embryonic development is crucial for advancing our knowledge of congenital cardiac malformations and designing new regenerative therapies. By combining genetic labelling, single-cell transcriptomics, and ex vivo human-mouse embryonic chimeras we uncovered that modulation of retinoic acid signaling instructs human pluripotent stem cells to form heart field-specific progenitors with distinct fate potentials. In addition to the classical first and second heart fields, we observed the appearance of juxta-cardiac field progenitors giving rise to both myocardial and epicardial cells. Applying these findings to stem-cell based disease modelling we identified specific transcriptional dysregulation in first and second heart field progenitors derived from stem cells of patients with hypoplastic left heart syndrome. This highlights the suitability of our in vitro differentiation platform for studying human cardiac development and disease.

Suggested Citation

  • Dorota Zawada & Jessica Kornherr & Anna B. Meier & Gianluca Santamaria & Tatjana Dorn & Monika Nowak-Imialek & Daniel Ortmann & Fangfang Zhang & Mark Lachmann & Martina Dreßen & Mariaestela Ortiz & Vi, 2023. "Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36764-x
    DOI: 10.1038/s41467-023-36764-x
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    References listed on IDEAS

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