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E-GEOD-6443

ABSTRACT: Transcription profiling of jejunums from wild type and Klf9-/- mice to investigate the involvement of Klf9 in small intestine crypt-villus cell renewal and lineage determination.

OTHER RELATED OMICS DATASETS IN: PRJNA99535

PROVIDER: E-GEOD-6443 | ExpressionAtlas | 2014-07-03

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-GEOD-6443-analysis-methods.tsv	Tabular
	E-GEOD-6443-atlasExperimentSummary.Rdata	Rdata
	E-GEOD-6443-configuration.xml	Xml
	E-GEOD-6443-percentile-ranks.tsv	Tabular
	E-GEOD-6443.condensed-sdrf.tsv	Tabular

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Project description:The peroxisome proliferator-activated receptor alpha (PPARÎ±) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPARÎ± in the small intestine. Since this organ is frequently exposed to high levels of PPARÎ± ligands via the diet, we set out to characterize the function of PPARÎ± in small intestine using functional genomics experiments and bioinformatics tools. PPARÎ± was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPARÎ± was expressed highest in villus cells of proximal jejunum. Microarray analyses of total tissue samples revealed, that in addition to genes involved in fatty acid and triacylglycerol metabolism, transcription factors and enzymes connected to sterol and bile acid metabolism, including FXR and SREBP1, were specifically induced. In contrast, genes involved in cell cycle and differentiation, apoptosis, and host defense were repressed by PPARÎ± activation. Additional analyses showed that intestinal PPARÎ± dependent gene regulation occurred in villus cells. Functional implications of array results were corroborated by morphometric data. The repression of genes involved in proliferation and apoptosis was accompanied by a 22% increase in villus height, and a 34% increase in villus area of wild-type animals treated with WY14643. This is the first report providing a comprehensive overview of processes under control of PPARÎ± in the small intestine. We show that PPARÎ± is an important transcriptional regulator in small intestine, which may be of importance for the development of novel foods and therapies for obesity and inflammatory bowel diseases. Experiment Overall Design: Pure bred wild-type (129S1/SvImJ) and PPARÎ±-null (129S4/SvJae) mice were treated with the synthetic PPARÎ± ligand WY14,643 (0.1% w/w) for 5 days. The complete intestines were then removed and total RNA was isolated. Experiment Overall Design: In total 4 experimental groups were present: wild type mice fed the control diet (AIN93M), wild type mice fed the control diet supplemented with 0.1% w/w WY14,643 for 5 days, PPARÎ± knockout mice fed the control diet, PPARÎ± knockout mice fed the control diet supplemented with 0.1% w/wWY14,643 for 5 days. Experiment Overall Design: RNA of 3 biological replicates was hybridized to Affymetrix 430A arrays. Experiment Overall Design: Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.

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E-GEOD-6443

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