Sox7‐positive endothelial progenitors establish coronary arteries and govern ventricular compaction

Chiang, Ivy KN and Humphrey, David and Mills, Richard J and Kaltzis, Peter and Pachauri, Shikha and Graus, Matthew and Saha, Diptarka and Wu, Zhijian and Young, Paul and Sim, Choon Boon and Davidson, Tara and Hernandez‐Garcia, Andres and Shaw, Chad A and Renwick, Alexander and Scott, Daryl A and Porrello, Enzo R and Wong, Emily S and Hudson, James E and Red‐Horse, Kristy and del Monte‐Nieto, Gonzalo and Francois, Mathias (2023) Sox7‐positive endothelial progenitors establish coronary arteries and govern ventricular compaction. EMBO reports, 24 (10). ISSN 1469-221X

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The cardiac endothelium influences ventricular chamber development by coordinating trabeculation and compaction. However, the endothelial-specific molecular mechanisms mediating this coordination are not fully understood. Here, we identify the Sox7 transcription factor as a critical cue instructing cardiac endothelium identity during ventricular chamber development. Endothelial-specific loss of Sox7 function in mice results in cardiac ventricular defects similar to non-compaction cardiomyopathy, with a change in the proportions of trabecular and compact cardiomyocytes in the mutant hearts. This phenotype is paralleled by abnormal coronary artery formation. Loss of Sox7 function disrupts the transcriptional regulation of the Notch pathway and connexins 37 and 40, which govern coronary arterial specification. Upon Sox7 endothelial-specific deletion, single-nuclei transcriptomics analysis identifies the depletion of a subset of Sox9/Gpc3-positive endocardial progenitor cells and an increase in erythro-myeloid cell lineages. Fate mapping analysis reveals that a subset of Sox7-null endothelial cells transdifferentiate into hematopoietic but not cardiomyocyte lineages. Our findings determine that Sox7 maintains cardiac endothelial cell identity, which is crucial to the cellular cross-talk that drives ventricular compaction and coronary artery development.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 01 May 2024 04:20
Last Modified: 01 May 2024 04:20

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