Back to Search
Start Over
Sox7‐positive endothelial progenitors establish coronary arteries and govern ventricular compaction.
- Source :
- EMBO Reports; 10/9/2023, Vol. 24 Issue 10, p1-21, 21p
- Publication Year :
- 2023
-
Abstract
- 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. Synopsis: Sox7 is essential for endothelial and endocardial differentiation mostly via the modulation of coronary arteries formation and the instruction of cardiac ventricular compaction. Loss of SOX7 function in the cardiac endothelium causes both a lack of distal coronary arteries and a depletion of endocardial progenitors resulting in a non‐compaction cardiomyopathy phenotype.SOX7 maintains a pool of Gpc3/Sox9 double‐positive endocardial cells critical for physiological ventricular maturation and compaction.SOX7 directly modulates Cx40 enhancer activity and regulates arterial differentiation in developing coronary arteries. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1469221X
- Volume :
- 24
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- EMBO Reports
- Publication Type :
- Academic Journal
- Accession number :
- 172875821
- Full Text :
- https://doi.org/10.15252/embr.202255043