Valproic Acid Initiates Transdifferentiation of the Human Ductal
                    Adenocarcinoma Cell-line Panc-1 Into α-Like Cells

Sebastian Friedrich Petry; Naga Deepa Kandula; Stefan Günther; Christian Helker; Undraga Schagdarsurengin; Thomas Linn

doi:10.1055/a-1750-9190

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2022; 130(10): 638-651
DOI: 10.1055/a-1750-9190

Article

Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells

Sebastian Friedrich Petry ^*

¹Clinical Research Unit, Center of Internal Medicine, Medical Clinic and Polyclinic III, Justus Liebig University, Giessen, Germany

,

Naga Deepa Kandula^*

¹Clinical Research Unit, Center of Internal Medicine, Medical Clinic and Polyclinic III, Justus Liebig University, Giessen, Germany

,

Stefan Günther

²Bioinformatics and deep sequencing platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany

,

Christian Helker

³Cell Signaling and Dynamics, Department of Biology, Philipps University, Marburg, Germany

,

Undraga Schagdarsurengin

⁴Epigenetics of Urogenital System, Clinic and Polyclinic of Urology, Pediatric Urology and Andrology, Justus Liebig University, Giessen, Germany

,

Thomas Linn

¹Clinical Research Unit, Center of Internal Medicine, Medical Clinic and Polyclinic III, Justus Liebig University, Giessen, Germany

› Author Affiliations

Abstract

Non-mesenchymal pancreatic cells are a potential source for cell replacement. Their transdifferentiation can be achieved by triggering epigenetic remodeling through e. g. post-translational modification of histones. Valproic acid, a branched-chain saturated fatty acid with histone deacetylase inhibitor activity, was linked to the expression of key transcription factors of pancreatic lineage in epithelial cells and insulin transcription. However, the potential of valproic acid to cause cellular reprogramming is not fully understood. To shed further light on it we employed next-generation RNA sequencing, real-time PCR, and protein analyses by ELISA and western blot, to assess the impact of valproic acid on transcriptome and function of Panc-1-cells. Our results indicate that valproic acid has a significant impact on the cell cycle, cell adhesion, histone H3 acetylation, and metabolic pathways as well as the initiation of epithelial-mesenchymal transition through acetylation of histone H3 resulting in α-cell-like characteristics. We conclude that human epithelial pancreatic cells can be transdifferentiated into cells with endocrine properties through epigenetic regulation by valproic acid favoring an α-cell-like phenotype.

Key words

pancreas - epigenetics - epithelial–mesenchymal transition

Full Text

References

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Supplementary Material