PuSH - Publication Server of Helmholtz Zentrum München

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)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Regulate Myocardial Proliferation; Cardiomyocyte Proliferation; Smooth-muscle; Differentiation; Lineage; Generation; Expression; Fibrosis; Organ
ISSN (print) / ISBN 1087-0156
e-ISSN 1546-1696
Journal Nature Biotechnology
Quellenangaben Volume: 41, Issue: 12, Pages: 1787-1800 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants European Research Council (ERC)
Deutsche Herzstiftung e.V.
Fondazione Umberto Veronesi funding
German Centre for Cardiovascular Research (DZHK)
German Research Foundation
European Research Council