VPA-treatment of Panc-1-cells to study epigenetic impact mediated by histone acetylation on epithelial-mesenchymal transmission

ABSTRACT: Non-mesenchymal pancreatic cells are a potential source for cell replacement therapies aiming to restore the endocrine capacity lost during diabetes mellitus. Although a highly complex network of transcription factors underlies the differentiation, growth, and specification of pancreatic precursors, several studies indicated that the transdifferentiation of non-mesenchymal cells can be achieved by epigenetic regulation. The induction of this epithelial-mesenchymal transition through the post-translational modification of histones, exerting control over both dynamic and long-term gene expression, is a promising approach for reprogramming them into mesenchymal cells. The small molecule and histone deacetylase inhibitor valproic acid was linked to the expression of key transcription factors of pancreatic lineage in epithelial cells and insulin transcription. However, the underlying mechanisms are not fully understood. To shed further light on the potential use of valproic acid for cellular reprogramming strategies, we studied its effects on human ductal Panc-1-cells employing next generation RNA sequencing, real-time PCR and protein analysis by ELISA and western blot. Our data indicate a significant regulation of cell cycle, cell adhesion, histone acetyltransferase and metabolism-related genes, and an epithelial–mesenchymal transition through acetylation of histone H3, resulting in the phenotype of a-cells, supporting the prospect of a therapeutic usage of epithelial pancreatic cells for the purpose of reprogramming into hormonesecreting endocrine cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166640 | GEO | 2022/02/07

REPOSITORIES: GEO