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Meier, A.B.* ; Zawada, D.* ; De Angelis, M.T.* ; Martens, L.D. ; Santamaria, G.* ; Zengerle, S.* ; Nowak-Imialek, M.* ; Kornherr, J.* ; Zhang, F.* ; Tian, Q.* ; Wolf, C.M.* ; Kupatt, C.* ; Sahara, M.* ; Lipp, P.* ; Theis, F.J. ; Gagneur, J. ; Goedel, A.* ; Laugwitz, K.L.* ; Dorn, T.* ; Moretti, A.*

Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease.

Nat. Biotechnol. 41, 1787-1800 (2023)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth and repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids that display retinoic acid-dependent morphological, molecular and functional patterning of the epicardium and myocardium typical of the left ventricular wall. By combining lineage tracing, single-cell transcriptomics and chromatin accessibility profiling, we describe the specification and differentiation process of different cell lineages in epicardioids and draw comparisons to human fetal development at the transcriptional and morphological levels. We then use epicardioids to investigate the functional cross-talk between cardiac cell types, gaining new insights into the role of IGF2/IGF1R and NRP2 signaling in human cardiogenesis. Finally, we show that epicardioids mimic the multicellular pathogenesis of congenital or stress-induced hypertrophy and fibrotic remodeling. As such, epicardioids offer a unique testing ground of epicardial activity in heart development, disease and regeneration.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Regulate Myocardial Proliferation; Cardiomyocyte Proliferation; Smooth-muscle; Differentiation; Lineage; Generation; Expression; Fibrosis; Organ
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 1087-0156
e-ISSN 1546-1696
Zeitschrift Nature Biotechnology
Quellenangaben Band: 41, Heft: 12, Seiten: 1787-1800 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503800-001
Förderungen European Research Council (ERC)
Deutsche Herzstiftung e.V.
Fondazione Umberto Veronesi funding
German Centre for Cardiovascular Research (DZHK)
German Research Foundation
European Research Council
DOI 10.1038/s41587-023-01718-7
WOS ID 000962355400002
Scopus ID 85151459757
PubMed ID 37012447
Erfassungsdatum 2023-10-06
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