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Cardioids reveal self-organizing principles of human cardiogenesis
Open accessPublished version of a preprint
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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“While demonstrating a large leap in self-assembling capabilities, these cardioids still relied heavily on complex growth factor mixtures, co-culture approaches to include epicardial clusters, and independent differentiation protocols to achieve their final results.”
From Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease (2021) · cites this paper as [20]
In the citing paper
“cardioids (an alternative nomenclature for heart or cardiac organoids) have been reported with a large internal chamber, relevant cardiac cell lineages and single cell transcriptomic analysis20.”
From Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease (2021) · cites this paper as [20]
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Metadata
- 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
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 184
- Issue
- 12
- Pages
- 3299-3317.e22
- ISSN
- 0092-8674 (ISSN-L)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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