Phenotype images of the developing heart from wild type and Sox7 mutant mouse embryo

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 identified 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
identified the depletion of a subset of Sox9/Gpc3 positive endocardial
progenitor cells and an increase in erythro-myeloid cell lineages. Fate
mapping analysis revealed 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.