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Title:
Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools | Nature Communications
Description:
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. The heart is formed from several spatiotemporally distinct progenitor pools during development. Here they show that modulation of retinoic acid signaling can instruct human pluripotent stems cells into heart progenitors that are useful for studying human development and disease.
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nature portfolio io/github/miccec/yagst/ privacy policy statistical programming language supplementary movie 1 section view tools reporting summary advertising single-cell rna-seq data stem cell research single-cell sequencing libraries fastq files multimodal single-cell data reprints ds=chi-10x-mouse-cardiomyocytes nature 572 nature nature 593 german research foundation source data file human ipsc-derived organoids mann-whitney-wilcoxon test depending hlhs patient-specific cms40 european research council bud/early bud stage called juxta-cardiac field human hlhs-derived cpc-ra+ bmp10 signaling promotes heart-field specific progenitors antisense-mediated exon skipping raw scrna-seq data published scrna-sequencing datasets scrna-seq data generated poly-l-lysine coated slides hlhs patients-derived hipscs processed scrna-seq data titin-based dilated cardiomyopathy solutions depending dehydration solutions patient-specific cms arising heart field-specific differences pluripotent stem cells hlhs-derived cpc-ra− integrated murine jagged1/notch signaling hpsc-derived cardiovascular progenitors cell current-clamp recording myocytic hlhs-derived cpc-ra+ confirmed proper reporting assessing atrial‐selective pharmacology assessing atrial-selective pharmacology
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headline:Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools
description: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. The heart is formed from several spatiotemporally distinct progenitor pools during development. Here they show that modulation of retinoic acid signaling can instruct human pluripotent stems cells into heart progenitors that are useful for studying human development and disease.
datePublished:2023-04-03T00:00:00Z
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Disease model
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headline:Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools
description: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. The heart is formed from several spatiotemporally distinct progenitor pools during development. Here they show that modulation of retinoic acid signaling can instruct human pluripotent stems cells into heart progenitors that are useful for studying human development and disease.
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multidisciplinary
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name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:Department of Experimental and Clinical Medicine, University âMagna Graeciaâ, Catanzaro, Italy
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:Department of Surgery, University of Cambridge, Cambridge, UK
name:Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:German Heart Center Munich, Department of Cardiovascular Surgery, Institute Insure - Technical University of Munich, School of Medicine and Health, Munich, Germany
name:Department of Surgery, University of Cambridge, Cambridge, UK
name:Bristol Heart Institute, Bristol Medical School, Translational Health Sciences, Bristol, UK
name:School of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, UK
name:Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Department of Experimental and Clinical Medicine, University âMagna Graeciaâ, Catanzaro, Italy
name:Department of Obstetrics and Gynecology, Stanford School of Medicine, Stanford University, Stanford, USA
name:Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany
name:Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany
name:Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:Department of Surgery, Yale University School of Medicine, New Haven, USA
name:First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
name:Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
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