Boles, Nathan C., Fernandes, Marie, Swigut, Tomasz, Srinivasan, Rajini, Schiff, Lauren ORCID: 0000-0003-2438-2456, Rada-Iglesias, Alvaro, Wang, Qingjie, Saini, Janmeet S., Kiehl, Thomas, Stern, Jeffrey H., Wysocka, Joanna, Blenkinsop, Timothy A. and Temple, Sally (2020). Epigenomic and Transcriptomic Changes During Human RPE EMT in a Stem Cell Model of Epiretinal Membrane Pathogenesis and Prevention by Nicotinamide. Stem Cell Rep., 14 (4). S. 631 - 648. CAMBRIDGE: CELL PRESS. ISSN 2213-6711

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Abstract

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 (PVR). We found that co-treatment with TGF-beta and TNF-alpha, (TNT) accelerates EMT in adult human RPE stem cell-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 key transcriptional changes, and inhibits and partially reverses RPE EMT, revealing potential therapeutic routes to benefit patients with ERM, macular pucker and PVR.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Boles, Nathan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandes, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swigut, TomaszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Srinivasan, RajiniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiff, LaurenUNSPECIFIEDorcid.org/0000-0003-2438-2456UNSPECIFIED
Rada-Iglesias, AlvaroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QingjieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saini, Janmeet S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiehl, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stern, Jeffrey H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wysocka, JoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blenkinsop, Timothy A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Temple, SallyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-337191
DOI: 10.1016/j.stemcr.2020.03.009
Journal or Publication Title: Stem Cell Rep.
Volume: 14
Number: 4
Page Range: S. 631 - 648
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2213-6711
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EPITHELIAL-MESENCHYMAL TRANSITION; PROLIFERATIVE VITREORETINOPATHY; RISK-FACTORS; PIGMENT-EPITHELIUM; GENE-EXPRESSION; PROGRESSION; BETAMultiple languages
Cell & Tissue Engineering; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33719

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