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Series GSE123501 Query DataSets for GSE123501
Status Public on Feb 05, 2019
Title Retinoic acid receptor alpha represses a Th9 transcriptional and epigenomic program to reduce allergic pathology
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary T helper (Th) differentiation is regulated by diverse inputs including the Vitamin A metabolite retinoic acid (RA). RA acts through its receptor RAR to repress transcription of inflammatory cytokines, but it is also essential for Th-mediated immunity, pointing to complex effects of RA in Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during differentiation of CD4+ T cells to multiple Th subsets. RA effects were subset-selective, and quantitatively greatest in Th9 cells. RA globally antagonized Th9-promoting transcription factors (TFs) and inhibited Th9 differentiation. RA directly targeted the extended Il9 locus and broadly modified the Th9 epigenome through RARa. RA-RARaactivity limited Th9-associated pulmonary inflammation in mice, and allergic inflammation in humans was associated with reduced expression of RA target genes. Thus, repression of the Th9 program is a major function of RA-RARa signaling in Th differentiation, arguing for a role for RA in IL-9 related diseases.
 
Overall design Integrated analysis of epigenome and transcriptome data from Th subsets treated with vehicle control or retinoic acid, and of in vivo Th subsets from papain-sensitized mice
 
Contributor(s) Schwartz DS, Meylan F, Shih HY, Mikami Y, Petermann FP, Sun HW, Yao CY, Jiang K, Davis FP, Kanno Y, O'Shea JJ
Citation(s) 30650370
Submission date Dec 07, 2018
Last update date Mar 21, 2019
Contact name Hong-wei Sun
Organization name NIAMS
Department Office of Science & Technology
Lab Biodata Mining & Discovery Section
Street address 9000 Rockville Pile
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (3)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (136)
GSM3505589 RARA_flox_CD4_WT_Th9_rep1
GSM3505590 RARA_flox_CD4_WT_Th9_RA_rep1
GSM3505591 RARAdCD4_Th9_rep1
Relations
BioProject PRJNA508954
SRA SRP173192

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
GSE123501_RAW.tar 44.3 Mb (http)(custom) TAR (of TXT)
GSE123501_RNA-Seq_R01-R16_rpkm.xlsx.gz 5.5 Mb (ftp)(http) XLSX
GSE123501_RNA-Seq_R17-R22_rpkm.xlsx.gz 2.8 Mb (ftp)(http) XLSX
GSE123501_RNA-Seq_R23-R70_rpkm.xlsx.gz 14.6 Mb (ftp)(http) XLSX
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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