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Series GSE206493 Query DataSets for GSE206493
Status Public on Apr 05, 2023
Title Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Although oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells can escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors for escape from OIS and identify ‘senescence-associated chromatin scars (SACS)’ as an epigenetic memory of OIS, detectable during colorectal cancer progression. POU2F2 levels are elevated already in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape to promote senescence escape and reveal POU2F2 gene signatures and SACS as valuable biomarkers with diagnostic and prognostic potential.
 
Overall design RNA-seq of GM21 human skin fibroblasts at days 14 and 27 after overexpression of H-RAS-G12V expressing control (non-targeting pLKO) or POU2F2-targeting (shPOU2F2 #324 and #325) shRNAs
 
Contributor(s) Zamudio RI, Stefa A, Nabuco JA, Vasilopoulos T, Simpson M, Doré G, Roux P, Galan MA, Chokshi RJ, Bischof O, Herbig U
Citation(s) 37082139
Submission date Jun 20, 2022
Last update date May 12, 2023
Contact name Ricardo Iván Martínez Zamudio
E-mail(s) rm1238@rwjms.rutgers.edu
Organization name Rutgers Biomedical and Health Sciences | Rutgers-Robert Wood Johnson Medical School
Department Pharmacology
Lab Martínez Zamudio Lab
Street address 675 Hoes Lane West
City Piscataway
State/province New Jersey
ZIP/Postal code 08854
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM6255295 GM21 fibroblasts, pLKO, Day 14 post RAS overexpression rep1
GSM6255296 GM21 fibroblasts, pLKO, Day 14 post RAS overexpression rep2
GSM6255297 GM21 fibroblasts, shPOU2F2 #324, Day 14 post RAS overexpression rep1
This SubSeries is part of SuperSeries:
GSE206496 Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars
Relations
BioProject PRJNA851072

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
GSE206493_Counts_POU2F2_KD.txt.gz 1.6 Mb (ftp)(http) TXT
GSE206493_RAW.tar 368.4 Mb (http)(custom) TAR (of BW)
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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