 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 11, 2016 |
| Title |
Ileal pouch transcriptomics reveal shared pathogenesis between pouchitis and ulcerative colitis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
UC pouchitis is a potential model of UC. We prospectively examined the pouch transcriptomes of UC and familial adenomatous polyposis (FAP) IPAA patients to unveil molecular mechanisms of UC pouchitis susceptibility.
Methods: Total RNA was isolated using the AllPrep DNA/RNA Mini Kit (QIAGEN, Cat No. 8020). RNA quality was evaluated using Bioanalyzer (Agilent, Santa Clara, CA). All RNA samples displayed RNA Integrity Number (RIN) >7. RNAseq including cDNA library preparation was processed at the Genomics Core Facility of University of Chicago (https://fgf.uchicago.edu/). Total RNA in the amount of 100-500μg per sample was depleted of ribosomal RNA using the Ribo-Zero kit (Epicentre, Madison, WI). The directional (first strand) cDNA libraries were prepared following the guide of TruSeq Stranded Total RNA Sample Preparation kit.
Results: Unlike FAP patients, UC subjects exhibited a large set of differentially expressed genes (DEGs) between pouch and pre-pouch mucosa as early as 4 months after pouch functionalization. Functional pathway analysis of DEGs in UC pouch revealed: (1) Gain of colon-associated gene expressions and loss of ileum associated gene expressions, (2) enhanced state of immune/inflammatory response, and (3) suppressed xenobiotic, lipid, and bile acid metabolic pathways. These changes were corroborated upon reanalysis of a published larger cross-sectional study of UC and FAP patients. Moreover, >70% of DEGs mapped to published IBD and normal colonic microarray datasets displayed directional changes consistent with active UC, but not Crohn's disease.
Conclusions: UC patients exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease. The transcriptome alterations provide insights into pouchitis
|
| |
|
| Overall design |
Seventeen patients with UC and four patients with FAP were recruited at the University of Chicago and the Mayo Clinic Rochester. All patients underwent a total proctocolectomy with ileal pouch anal anastomosis (IPAA) as a standard of care. UC patients underwent a pouchoscopy for biopsy of the pre-pouch ileum and pouch at 4 months, 8 months, and 12 months after ileostomy closure. None of these patients had pouchitis.
|
| |
|
| Contributor(s) |
Huang Y, Dalal S, Chang EB |
| Citation(s) |
28221248 |
| |
| Submission date |
May 10, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Yong Huang |
| E-mail(s) |
[email protected]
|
| Phone |
(434) 243-0842
|
| Organization name |
University of Viginia
|
| Department |
Medicine
|
| Street address |
1340 Jefferson Park Ave
|
| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (77)
|
|
| Relations |
| BioProject |
PRJNA321131 |
| SRA |
SRP074739 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE81266_Pouch.combat.txt.gz |
5.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...