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Coordination of cardiogenesis in vivo and in vitro

Nature Reviews Molecular Cell Biology (2025)Cite this article

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Abstract

Heart development has been extensively explored on the anatomical, cellular and molecular levels. Yet, the intricate interplay of tissue organization, cellular lineages and molecular factors that orchestrate heart development, culminating in forming a seamlessly synchronized functional heart, remains challenging to investigate. Mechanistic studies conducted both in vivo using animal models and in vitro stem-cell-derived systems aim to unravel this complexity. In this Review, we discuss how the recent surge in technological advancements in imaging and genomics, coupled with the evolution of next-generation cardiac organoid models, has provided profound insights into these processes, holding significant implications for the development of novel therapies for congenital or acquired heart diseases. We discuss the development of the heart as the first functional organ — from the morphogenesis of the mesoderm, heart tube and cardiac chambers to the establishment of the initial heartbeat and pacemaker and further how morphogenesis and function collaboratively drive heart maturation.

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Fig. 1: Coordination of cardiogenesis in vivo and in vitro.
Fig. 2: Early human cardiogenesis.
Fig. 3: Development of electrophysiological conduction and cardiac functionality.
Fig. 4: Pacemaking dominance and developmental speed of conduction velocity.
Fig. 5: Biomechanical cues influence valve formation and trabeculation.

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Authors and Affiliations

  1. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria

    Sasha Mendjan & Alison Deyett

  2. Division of Cell Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria

    Sasha Mendjan

  3. Vienna Biocenter PhD Program, Doctoral School of the University of Vienna and the Medical University of Vienna, Vienna, Austria

    Alison Deyett

  4. Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA

    Deborah Yelon

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Correspondence to Sasha Mendjan.

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Competing interests

IMBA filed a patent application (No. 21712188.8) on multichamber cardioids with A.D. and S.M. named as inventors. S.M. is a co-founder of HeartBeat.bio. D.Y. declares no competing interests.

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Mendjan, S., Deyett, A. & Yelon, D. Coordination of cardiogenesis in vivo and in vitro. Nat Rev Mol Cell Biol (2025). https://doi.org/10.1038/s41580-025-00878-5

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