ETV2 Upregulation Marks the Specification of Early Cardiomyocytes and Endothelial Cells During Co-differentiation.
CRISPR/Cas9
ETV2
ETV2-mCherry fluorescent stem cell reporter
RNA sequencing
cardiac differentiation
hiPSC-derived endothelial cells
human induced pluripotent stem cells (hiPSCs)
single-cell RNA sequencing
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
02 03 2023
02 03 2023
Historique:
received:
21
05
2022
accepted:
01
12
2022
pubmed:
14
12
2022
medline:
7
3
2023
entrez:
13
12
2022
Statut:
ppublish
Résumé
The ability to differentiate human-induced pluripotent stem cells (hiPSCs) efficiently into defined cardiac lineages, such as cardiomyocytes and cardiac endothelial cells, is crucial to study human heart development and model cardiovascular diseases in vitro. The mechanisms underlying the specification of these cell types during human development are not well understood which limits fine-tuning and broader application of cardiac model systems. Here, we used the expression of ETV2, a master regulator of hematoendothelial specification in mice, to identify functionally distinct subpopulations during the co-differentiation of endothelial cells and cardiomyocytes from hiPSCs. Targeted analysis of single-cell RNA-sequencing data revealed differential ETV2 dynamics in the 2 lineages. A newly created fluorescent reporter line allowed us to identify early lineage-predisposed states and show that a transient ETV2-high-state initiates the specification of endothelial cells. We further demonstrated, unexpectedly, that functional cardiomyocytes can originate from progenitors expressing ETV2 at a low level. Our study thus sheds light on the in vitro differentiation dynamics of 2 important cardiac lineages.
Identifiants
pubmed: 36512477
pii: 6895495
doi: 10.1093/stmcls/sxac086
pmc: PMC9982073
doi:
Substances chimiques
ETV2 protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
140-152Informations de copyright
© The Author(s) 2022. Published by Oxford University Press.
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