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Distinct human stem cell populations in small and large intestine

ABSTRACT: The intestine is composed of an epithelial layer, containing rapidly proliferating cells that mature into two distinct anatomic regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for the whole intestine, no studies have compared stem cells derived from the small and large intestine. Here, we report intrinsic differences between these two populations of cells. Primary epithelial cells isolated from human fetal small and large intestine and expanded with Wnt agonist, R-spondin 2, displayed differential expression of stem cell markers and separate hierarchical clustering of gene expression involved in differentiation, proliferation and disease pathways. Using a three-dimensional in vitro differentiation assay, single cells derived from small and large intestine formed distinct organoid architecture with cellular hierarchy similar to that found in primary tissue. Our characterization of human fetal intestinal stem cells defies the classical definition proposed by most where small and large intestine are repopulated by an identical epithelial stem cell and raises the question of the importance of intrinsic and extrinsic cues in the development of intestinal diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56525 | GEO | 2015/01/15

SECONDARY ACCESSION(S): PRJNA243625

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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Distinct human stem cell populations in small and large intestine

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