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Series GSE67898 Query DataSets for GSE67898
Status Public on Jul 06, 2015
Title Reversal of persistent wound-induced retinal pigmented epithelial-to-mesenchymal transition by the TGFb pathway inhibitor, A-83-01.
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Age-related macular degeneration (AMD) is a leading cause of blindness. Most vision loss occurs following the transition from a disease of deposit formation and inflammation to a disease of neovascular fibrosis and/or cell death. Here, we investigate how repeated wound stimulus leads to seminal changes in gene expression and the onset of a perpetual state of stimulus-independent wound response in retinal pigmented epithelial (RPE) cells, a cell-type central to the etiology of AMD. Using a human fetal RPE cell culture model that considers monolayer disruption and subconfluent culture as a proxy for wound stimulus, we have shown that prolonged wound stimulus leads to terminal acquisition of a mesenchymal phenotype post-confluence and altered expression of more than 40% of the transcriptome (see GEO:GSE62224). In contrast, at subconfluence fewer than 5% of expressed transcripts have 2-fold or greater expression differences after repeated passage. Protein-protein and pathway interaction analysis of the genes with passage-dependent expression levels in subconfluent cultures reveals a 158-node interactome comprised of two interconnected modules with functions pertaining to wound response and cell division. Among the wound response genes are the TGFb pathway activators: TGFB1, TGFB2, INHBA, INHBB, GDF6, CTGF, and THBS1. Significantly, inhibition of TGFBR1/ACVR1B mediated signaling using receptor kinase inhibitors both forestalls and reverses the passage-dependent loss of epithelial potential. In this RNA-Seq based transcriptome analysis we show that the TGFb receptor kinase inhibitor, A-83-01, largely reverses the effects of passage and restores the transcriptome profile of Passage 4 RPE highly similar to that seen in differentiated Passage 0 RPE.
 
Overall design Examination of mRNA expression in three different primary fetal RPE donor lines in 32 day old passage 0, passage 3, and passage 3 treated with 500 nM A-83-01 culutres
 
Contributor(s) Radeke MJ, Radeke CM, Shih Y, Coffey P
Citation(s) 26150894
Submission date Apr 15, 2015
Last update date May 15, 2019
Contact name Monte J. Radeke
E-mail(s) radeke@ucsb.edu
Phone 805-893-3695
Organization name University of California, Santa Barbara
Department Neuroscience Research Institute
Lab Center for the Study of Macular Degeneration
Street address Neuroscience Research Institiute
City Santa Barbara
State/province CA
ZIP/Postal code 93106-5060
Country USA
 
Platforms (2)
GPL17301 Ion Torrent PGM (Homo sapiens)
GPL17303 Ion Torrent Proton (Homo sapiens)
Samples (10)
GSM1657677 RPEA_P0_D32
GSM1657678 RPEB_P0_D32
GSM1657679 RPEC_P0_D32_1
This SubSeries is part of SuperSeries:
GSE67899 Delay and restoration of persistent wound-induced retinal pigmented epithelial-to-mesenchymal transition by TGF-beta pathway inhibitors: Implications for age-related macular degeneration
Relations
BioProject PRJNA281448
SRA SRP057295

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE67898_Passage_A83_matrix.txt.gz 960.8 Kb (ftp)(http) TXT
GSE67898_RAW.tar 3.9 Mb (http)(custom) TAR (of TXT)
GSE67898_RPEC_P0_D32.txt.gz 498.3 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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