Cardiomyocyte-specific TGFb1/2/3 deficiency impacts early heart maturation [snRNA-Seq].

The fibroblasts, in turn, impact cardiomyocyte maturation through cell-cell interactions, ECM-cellular interactions, and paracrine factors. We observed that the combined deletion of Tgfb1, Tgfb2, Tgfb3 genes (TGFβ ligands) from cardiomyocytes in the early developing heart results in cardiac dysfunction by 6 weeks of age with altered fibroblast activity and perturbed ECM content.

Effects were however apparent far earlier, with postnatal hearts being dysmorphic and cardiac fibroblasts having incorrect activity, producing inappropriate ECM with reduced stiffness. This indicating effects during early development, both embryonic and post-natal. In order to elucidate these early effects, we carried out single nucleus RNA sequencing analysis of cardiac nuclei isolated from experimental (lacking TGFβ1/2/3 in cardiac myocytes) and control (expressing TGFβ1/2/3 in cardiac myocytes) hearts harvested from P7 (day 7 post-birth) pups.