Endocardial TIE1 synergizes with TIE2 to regulate the atrial internal muscular network assembly [RNA-Seq heart atria ventricle]

Consistent with the scRNA-seq data, we found that Tie1 and Tek transcripts were higher in atria than in ventricles. Furthermore, the endothelial deletion of Tek resulted in the defective formation of cardiac trabeculae, particularly in atria. Consistently, the loss of Tie1 combined with one null allele of Tek disrupted both atrial and ventricular trabeculation.

Surprisingly, defects with the atrial chamber morphogenesis were already detectable 48 hours later upon the induced endothelial loss of Tie1 plus the Tek heterozygous deletion, implying a critical role of endocardium in the organization of the atrial internal muscular network. The synergy of TIE1 and TIE2 in the remodeling of atrial trabeculae was further confirmed at the postnatal stage, while TIE1 insufficiency alone had no obvious effect.

Together, findings from this study imply that TIE1 is differentially required for the atrial and ventricular development and acts in synergy with TIE2 to regulate the endocardial cell-coordinated atrial internal muscular network assembly.