Cited by 592Pluripotent Stem Cells ResearchCongenital heart defects researchTissue Engineering and Regenerative Medicine

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Cardioids reveal self-organizing principles of human cardiogenesis

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Hofbauer, Pablo, Jahnel, Stefan M., Papai, Nora, Giesshammer, Magdalena, Deyett, Alison, Schmidt, Clara, Penc, Mirjam, Tavernini, Katherina, Grdseloff, Nastasja, Meledeth, Christy, Ginistrelli, Lavinia Ceci, Ctortecka, Claudia, Šalic, Šejla, Novatchkova, Maria, Mendjan, Sasha·2021·Cell

DOI 10.1016/j.cell.2021.04.034

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Abstract

Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.

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Authors: Hofbauer, P., Jahnel, S. M., Papai, N., Giesshammer, M., Deyett, A., Schmidt, C., Penc, M., Tavernini, K., Grdseloff, N., Meledeth, C., Ginistrelli, L. C., Ctortecka, C., Šalic, Š., Novatchkova, M., & Mendjan, S.
Affiliations: Institute of Molecular Biotechnology (AT)
Research Institute of Molecular Pathology (AT)
Corresponding author: Mendjan, Sasha
ORCID: Jahnel, Stefan M.
Deyett, Alison
Tavernini, Katherina
Grdseloff, Nastasja
Meledeth, Christy
Ginistrelli, Lavinia Ceci
Ctortecka, Claudia
Novatchkova, Maria
Mendjan, Sasha
Venue: Cell
Publisher: Elsevier BV
Published: 2021-06
Volume: 184
Issue: 12
Pages: 3299-3317.e22
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2021.04.034
OpenAlex: W3161466741
Cited by: 588
References: 119
Citations by year: 2026: 121 · 2025: 130 · 2024: 118 · 2023: 92 · 2022: 90 · 2021: 35
FWCI: 26.74
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
PubMed (publishedVersion)
Funders: FFG
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords: cardioid, heart development, self-organization, human pluripotent stem cells, HAND1, extracellular matrix accumulation, cryoinjury, congenital heart disease, cardiac regeneration
MeSH terms: Homeobox Protein Nkx-2.5, Animals, Calcium, Cell Line, Chickens, Female, Fibroblasts, Heart, Humans, Male, Mesoderm, Models, Biological, Myocardium, Organoids, Extracellular Matrix Proteins, Cell Lineage, Bone Morphogenetic Proteins, Activins, Organogenesis, Pluripotent Stem Cells, Vascular Endothelial Growth Factor A, Endothelial Cells, Wnt Proteins, Basic Helix-Loop-Helix Proteins

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Cardioids reveal self-organizing principles of human cardiogenesis

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