Global Epigenomic and Transcriptomic changes associated with Human Retinal Pigment Epithelial Epithelial-to-Mesenchymal Transition in a Stem Cell-based model of Epiretinal Membrane Formation (RNA-seq)

Epithelial to mesenchymal transition (EMT) is a biological process involved in tissue morphogenesis and disease that causes dramatic changes in cell morphology, migration, proliferation, and gene expression. The retinal pigment epithelium (RPE), which supports the neural retina, can undergo EMT, producing fibrous epiretinal membranes (ERMs) associated with vision-impairing clinical conditions such as macular pucker and proliferative vitreoretinopathy. We found that co-treatment with TGFß1 and TNFa (TNT) accelerates EMT in adult human RPE stem cell (RPESC)-derived RPE cell cultures. We captured the global epigenomic and transcriptional changes elicited by TNT treatment of RPE and identified putative active enhancers associated with actively transcribed genes, including a set of upregulated transcription factors that are candidate regulators. We found that the vitamin B derivative nicotinamide downregulates these factors, inhibits key transcriptional changes and prevents and partially reverses RPE EMT, revealing potential therapeutic routes to benefit patients with ERM, macular pucker and PVR. Overall design: Poly-A enriched RNAseq from retinal pigmented epithelial cells from two donors, either in control culture condition or treated with TNF-alpha and TGF-beta