Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of Paneth cells and whole ileum from human Crohn's disease patient ileo-colic resection tissue

ABSTRACT: Transcriptional profiling of microscopically laser dissected Paneth cells and whole thickness ileum tissue from the proximal margins of archived formalin-fixed, paraffin-embedded ileo-colic resection samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Kelli VanDussen

PROVIDER: E-MTAB-1281 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genetic variants synthesize to produce paneth cell phenotypes that define subtypes of Crohn's disease.

VanDussen Kelli L KL Liu Ta-Chiang TC Li Dalin D Towfic Fadi F Modiano Nir N Winter Rachel R Haritunians Talin T Taylor Kent D KD Dhall Deepti D Targan Stephan R SR Xavier Ramnik J RJ McGovern Dermot P B DP Stappenbeck Thaddeus S TS

Gastroenterology 20130925 1

<h4>Background & aims</h4>Genetic susceptibility loci for Crohn's disease (CD) are numerous, complex, and likely interact with undefined components of the environment. It has been a challenge to link the effects of particular loci to phenotypes of cells associated with pathogenesis of CD, such as Paneth cells. We investigated whether specific phenotypes of Paneth cells associated with particular genetic susceptibility loci can be used to define specific subtypes of CD.<h4>Methods</h4>We performe ...[more]

PMID: 24076061

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Project description:BackgroundPaneth cell dysfunction has been implicated in a subset of Crohn's disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients.MethodsPediatric CD (n = 44) and non-IBD (n = 62) patients aged 4 to 18 were recruited prior to routine endoscopic biopsy. Ileal mucosal samples were analyzed for Paneth cell phenotypes, mucosal microbiome composition, and RNA transcriptome.ResultsThe prevalence of abnormal Paneth cells was higher in pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal Paneth cells showed significant changes in their ileal mucosal microbiome, highlighted by reduced protective microbes and enriched proinflammatory microbes. Ileal transcriptome profiles showed reduced transcripts for genes that control oxidative phosphorylation in CD patients with abnormal Paneth cells. These transcriptional changes in turn were correlated with specific microbiome alterations. In non-IBD patients, a subset contained abnormal Paneth cells. However, this subset was not associated with alterations in the microbiome or host transcriptome.ConclusionPaneth cell abnormalities in human subjects are associated with mucosal dysbiosis in the context of CD, and these changes are associated with alterations in oxidative phosphorylation, potentially in a feedback loop.FundingThe research was funded by Helmsley Charitable Trust (to T.S. Stappenbeck, R.J. Xavier, and D.P.B. McGovern), Crohn's and Colitis Foundation of America (to N.H. Salzman, T.S. Stappenbeck, R.J. Xavier, and C. Huttenhower), and Doris Duke Charitable Foundation grant 2014103 (to T.C. Liu).

Dataset Information

Transcription profiling by array of Paneth cells and whole ileum from human Crohn's disease patient ileo-colic resection tissue

Publications

Genetic variants synthesize to produce paneth cell phenotypes that define subtypes of Crohn's disease.

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