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Series GSE129172 Query DataSets for GSE129172
Status Public on Jan 01, 2020
Title Setdb1 safeguards genome stability against stem cell necroptosis and bowel inflammation (RNA-seq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The aetiology of bowel inflammatory disease (IBD) is a multifactorial interplay between heredity and environment1-3. Here we report SETDB1, a histone methyltransferase (HMTs) for histone H3 lysine 9 trimethylation (H3K9me3) whose deficiency participates in the pathogenesis of IBD. We found that SETDB1 level decreased in IBD patients and that mice with reduced SETDB1 in intestinal stem cells (ISCs) developed spontaneous terminal ileitis and colitis. SETDB1 safeguards genome stability4, of which the loss in ISCs released repression of endogenous retrovirus (ERVs), the retrovirus-like elements with long repeats that comprise ~8% of genome5. Excessive viral mimicry generated by motivated ERVs triggered Z-DNA-binding protein 1 (ZBP1) dependent necroptosis, which irreversibly disrupted the homeostasis of epithelial barrier and promoted bowel inflammation. Of note, genome instability, reactive ERVs, upregulation of ZBP1 and necroptosis were seen in IBD patients. Pharmaceutic inhibition of RIP3 showed curative effect in SETDB1 deficient mice, suggesting therapy targeting ISC necroptosis may represent a new approach for severe IBD treatment.
Overall design Crypts mRNA profiles of 8-weeks old wild type (setdb1fl/fl) and setdb1-iIEC-KO mice were generated by deep sequencing using BGI-500. ISC total mRNA from Lgr5–EGFP–ires–CreERT2;setdb1fl/+ and Lgr5–EGFP–ires–CreERT2;setdb1fl/fl were generated for deep sequencing using Hiseq X10.
Contributor(s) Li H, wang r
Citation(s) 32296174
Submission date Apr 02, 2019
Last update date Apr 21, 2020
Contact name hongda li
Organization name Xiamen University
Street address School of Life Sciences, Xiang'an Campus, Xiamen University, Xiang'an District, Xiamen, Fujian Province, China
City xiamen
ZIP/Postal code 361102
Country China
Platforms (2)
GPL21273 HiSeq X Ten (Mus musculus)
GPL23479 BGISEQ-500 (Mus musculus)
Samples (8)
GSM3701968 Crypts_WT
GSM3701969 Crypts_VEMD2
GSM3701970 Crypts_VEMD3
This SubSeries is part of SuperSeries:
GSE129174 Setdb1 safeguards genome stability against stem cell necroptosis and bowel inflammation
BioProject PRJNA530393
SRA SRP190122

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Supplementary file Size Download File type/resource
GSE129172_RNA_expression_ERVs.txt.gz 2.5 Kb (ftp)(http) TXT
GSE129172_RNA_expression_days.txt.gz 250.9 Kb (ftp)(http) TXT
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Processed data are available on Series record

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