Genomics,Multiomics

Dataset Information

3

Transcription profiling by array of intestinal epithelial cells (IECs) in germ-free conditions from mice with IEC-specific HDAC3 deletion against wild type controls


ABSTRACT: The development and severity of inflammatory bowel diseases (IBD) and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that intestinal epithelial cells (IECs) isolated from IBD patients exhibit decreased expression of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3). Further, genome-wide analyses of murine IECs that lack HDAC3 (HDAC3ΔIEC) revealed that HDAC3 deficiency resulted in dysregulated gene expression coupled with alterations in histone acetylation. Critically, conventionally-housed HDAC3ΔIEC mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3ΔIEC mice exhibited significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 plays a central role in maintaining intestinal homeostasis. Strikingly, rederivation of HDAC3ΔIEC mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis, and intestinal barrier function were largely restored in the absence of commensal bacteria. Collectively, these data indicate that the HDAC3 is a critical factor that integrates commensal bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis. In this study, we performed gene expression profiling to examine how the transcriptional profiles in primary live, EpCAM+ IECs from the large intestine differed between germ-free control HDAC3FF mice (3 biological replicates) and germ-free IEC-intrinsic knockout HDAC3ΔIEC mice (3 biological replicates).

REANALYSED by: E-GEOD-50189

OTHER RELATED OMICS DATASETS IN: PRJNA217044PRJNA217034E-GEOD-50188PRJNA217526PRJNA217043

ORGANISM(S): Mus musculus  

SUBMITTER: Theresa Alenghat   David Artis 

PROVIDER: E-GEOD-50189 | ArrayExpress | 2013-11-12

SECONDARY ACCESSION(S): GSE50189PRJNA217044

REPOSITORIES: GEO, ArrayExpress

Dataset's files

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Action DRS
E-GEOD-50189.idf.txt Idf
E-GEOD-50189.processed.1.zip Processed
E-GEOD-50189.raw.1.zip Raw
E-GEOD-50189.sdrf.txt Txt
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Publications


The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that mice with an intestinal epithelial cell (IEC)-specific deletion of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3(ΔIEC) mice) exhibited extensive dysregulation of IEC-intri  ...[more]

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