Human heart-forming organoids recapitulate early heart and foregut development.

Body Patterning Embryonic Development Gene Knockdown Techniques Green Fluorescent Proteins / genetics Heart / embryology Hepatocyte Nuclear Factor 4 / genetics Homeobox Protein Nkx-2.5 / genetics Humans Intestines / embryology Organoids / embryology SOXB1 Transcription Factors / genetics SOXF Transcription Factors / genetics Sequence Analysis, RNA

Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
06 2021
Historique:
received: 18 06 2019
accepted: 30 12 2020
pubmed: 10 2 2021
medline: 28 8 2021
entrez: 9 2 2021
Statut: ppublish

Résumé

Organoid models of early tissue development have been produced for the intestine, brain, kidney and other organs, but similar approaches for the heart have been lacking. Here we generate complex, highly structured, three-dimensional heart-forming organoids (HFOs) by embedding human pluripotent stem cell aggregates in Matrigel followed by directed cardiac differentiation via biphasic WNT pathway modulation with small molecules. HFOs are composed of a myocardial layer lined by endocardial-like cells and surrounded by septum-transversum-like anlagen; they further contain spatially and molecularly distinct anterior versus posterior foregut endoderm tissues and a vascular network. The architecture of HFOs closely resembles aspects of early native heart anlagen before heart tube formation, which is known to require an interplay with foregut endoderm development. We apply HFOs to study genetic defects in vitro by demonstrating that NKX2.5-knockout HFOs show a phenotype reminiscent of cardiac malformations previously observed in transgenic mice.

Identifiants

DOI: 10.1038/s41587-021-00815-9 PMID: 33558697 PMC: PMC8192303
pubmed: 33558697
doi: 10.1038/s41587-021-00815-9
pii: 10.1038/s41587-021-00815-9
pmc: PMC8192303
doi:

Substances chimiques

HNF4A protein, human 0
Hepatocyte Nuclear Factor 4 0
Homeobox Protein Nkx-2.5 0
NKX2-5 protein, human 0
SOX2 protein, human 0
SOXB1 Transcription Factors 0
SOXF Transcription Factors 0
enhanced green fluorescent protein 0
Green Fluorescent Proteins 147336-22-9

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

737-746

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

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Auteurs

Lika Drakhlis (L)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany. drakhlis.lika@mh-hannover.de.
ORCID: 0000-0003-2424-1127

Santoshi Biswanath (S)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Clara-Milena Farr (CM)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Victoria Lupanow (V)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Jana Teske (J)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Katharina Ritzenhoff (K)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Annika Franke (A)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Felix Manstein (F)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
ORCID: 0000-0001-9740-9686

Emiliano Bolesani (E)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.

Henning Kempf (H)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Stem Cell Discovery, Novo Nordisk A/S, Måløv, Denmark.
ORCID: 0000-0003-2790-9137

Simone Liebscher (S)

Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany.

Katja Schenke-Layland (K)

Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany.
The Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany.
Department of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', Eberhard Karls University Tübingen, Tübingen, Germany.
ORCID: 0000-0001-8066-5157

Jan Hegermann (J)

Research Core Unit Electron Microscopy, Hannover Medical School, Hannover, Germany.
Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.

Lena Nolte (L)

Industrial and Biomedical Optics Department, Laser Zentrum Hannover, Hannover, Germany.

Heiko Meyer (H)

Industrial and Biomedical Optics Department, Laser Zentrum Hannover, Hannover, Germany.

Jeanne de la Roche (J)

Institute for Neurophysiology, Hannover Medical School, Hannover, Germany.
ORCID: 0000-0001-5753-1732

Stefan Thiemann (S)

Institute for Neurophysiology, Hannover Medical School, Hannover, Germany.

Christian Wahl-Schott (C)

Institute for Neurophysiology, Hannover Medical School, Hannover, Germany.
ORCID: 0000-0002-7514-2367

Ulrich Martin (U)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Hannover, Germany.
ORCID: 0000-0003-1058-4540

Robert Zweigerdt (R)

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany. zweigerdt.robert@mh-hannover.de.
ORCID: 0000-0002-4656-0770

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Morphogenèse › Plan d'organisation du corps › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Développement embryonnaire et foetal › Développement embryonnaire › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-down de gènes › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines luminescentes › Protéines à fluorescence verte › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs nucléaires hépatocytaires › Facteur nucléaire hépatocytaire HNF-4 › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéine homéotique Nkx-2.5 › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Système digestif › Tube digestif › Intestins › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Tissus › Organoïdes › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription SOX › Facteurs de transcription SOX-B1 › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription SOX › Facteurs de transcription SOX-F › Human heart-forming organoids recapitulate...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Human heart-forming organoids recapitulate...