Ricerc@Sapienza

Background: Although adipose stromal cells (ASCs) retain the ability to transdifferentiate at low rate towards the cardiac lineage, the potential mechanisms underlying such process have still to be elucidated. Methods: Since chromatin state modifications are involved in several processes regulating the cellular cell fate commitment, we aimed at evaluating the role of histone protein acetylation in the cardiovascular-like transdifferentiation of ASCs. Results: We found a clear increase of histone 3 acetylation status paralleled by a significant upregulation of cardiac TnI gene expression, in ASCs treated with the conditioned medium of primary cardiomyocyte cell cultures for 72 hours. This result suggests that histone acetylation contributes to the transdifferantiation of ASCs towards the cardiac lineage. In order to directly test this hypothesis, ASCs cultured with regular medium were treated with SAHA, a pan histone deacetylase inhibitor. We found that SAHA enhanced the cardiac permissive state of ASCs, increasing both mRNA and protein expression of cardiovascular genes, particularly cTnI. This suggests that histone acetylation induction is sufficient to promote cardiovascular transdifferentiation. Conclusions: the control of ASC fate by epigenetic regulators might be an interesting tool to boost both cardiac commitment and regenerative capacities of ASCs.