Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
14
03
2022
accepted:
22
02
2023
pubmed:
4
4
2023
medline:
4
4
2023
entrez:
3
4
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37012447
doi: 10.1038/s41587-023-01718-7
pii: 10.1038/s41587-023-01718-7
pmc: PMC10713454
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1787-1800Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Transregio Research Unit 267
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Transregio Research Unit 152
Organisme : Deutsches Zentrum für Herz-Kreislaufforschung (Deutsches Zentrum für Herz-Kreislaufforschung e.V.)
ID : FKZ 81Z0600601
Informations de copyright
© 2023. The Author(s).
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