The role of charme in the phenotype and function of resident cardiac mesenchymal stromal cells

Abstract Background Charme is a murine long non-coding RNA with specific expression in striated muscles, presenting a human orthologue with 45% identity. Its depletion leads to incomplete muscle differentiation. Charme-/- mice display an altered cardiac phenotype with increased wall thickness and reduced chamber dimensions due to myocyte hyperplasia. Left ventricular dilatation and reduced fractional shortening are detected in aged Charme-/- mice. Embryonic myocardial architecture reveals aberrant compaction and ventricular hypotrabeculation, resembling some congenital cardiomyopathies. Cardiac mesenchymal stromal cells (CMSCs) play key roles in tissue homeostasis and pathophysiology, by maintaining the extracellular matrix and by paracrine action on all myocardial cells. Purpose To elucidate the phenotype, paracrine function, and myofibroblast differentiation capacity of resident CMSCs in the Charme-/- mouse model. Methods CMSCs were isolated from 5-week-old wild-type (WT) and Charme-/- mice by explant culture, pooling at least 4 different hearts per culture. Results Charme-/- CMSCs showed increased features of primitive phenotypes, such as enhanced spontaneous spheroid growth (123,6±11,9 vs 51,0±6,4 spheroids/well; N=8, p