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Effects of overexpressing HNF4A on 3D cultured mouse and human colon organoid

ABSTRACT: To test the hypothesis that HNF4A should engage small intestine enhancers in colon and activate transcription, we over-expressed HNF4A in 2 independent mouse colonic orgnaoid lines and 5 independent human colonic organoid lines and performed RNA-seq studies. Both RNA-seq data revealed that small intestine functional pathways including fat, protein and carbohydrate digestion and absorption were activated after HNF4A OE. This gain-of-function study of HNF4A in mouse and human colon organoid supports HNF4A as a central mediator of small intestine gene activation in colonic plasticity, conserved across species.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE245288 | GEO | 2024/03/08

REPOSITORIES: GEO

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Project description:Human intestinal epithelial organoids (IEO) culture models are rapidly emerging as novel experimental tools to investigate fundamental aspects of intestinal epithelial (patho)physiology. Cellular source and culture protocols vary between different IEO models and reliable markers for their characterization/validation are currently limited. DNA methylation has been demonstrated to play a key role in regulating gene expression and cellular function. This epigenetic mark is comparably stable and has been shown to reflect cellular identity such as tissue origin, developmental stage and age. Our genome wide DNA methylation datasets of purified human epithelium represent a unique resource, which can be used by other researchers to validate their model systems We provide the following datasets of genome-wide DNA methylation profiling by Infinium HumanMethylation450 BeadChip: Purified intestinal epithelial cells (EpCAM+) from paediatric ileum and colon, Non-epithelial mucosal cells (EpCAM-), Whole colonic mucosal biopsies, Intestinal organoid cultures from paediatric ileum and colon, Purified intestinal epithelial cells (EpCAM+) from foetal small intestine and foetal large intestine, Intestinal organoid cultures from foetal small intestine and foetal large intestine, Intestinal organoid cultures derived from induced pluripotent stem cells. Note: Some samples in this data set were previously submitted to ArrayExpress under accession number E-MTAB-3709. They're clearly marked in the âDescriptionâ field in sample annotations. Information about batch effect during sample handling is included in the experimental variable âblockâ. Batch effect is not massive but present, so it is recommended that batch correction is carried out in data analysis. Complementary RNA-seq data on the purified cells and organoids can be found in ArrayExpress at E-MTAB-5015 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5015/ ).

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Effects of overexpressing HNF4A on 3D cultured mouse and human colon organoid

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