Human small intestine
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA732897 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18746700_1.fastq.gz | Fastqsanger.gz | |||
| SRR18746700_2.fastq.gz | Fastqsanger.gz | |||
| SRR18746701_1.fastq.gz | Fastqsanger.gz | |||
| SRR18746701_2.fastq.gz | Fastqsanger.gz | |||
| SRR18746702_1.fastq.gz | Fastqsanger.gz |
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Project description: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. 12 samples were analyzed. They consisted of human fetal small and large intestine (SI; n=6 and LI; n=6) stem cells, expanded with Wnt agonist and R-spondin 2. Differential expression of genes in epithelial cells from both the large and small intestine were observed.
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Project description:Significant progress has been recently achieved in generating in vitro human small intestine models. Nonetheless, there remains ample opportunity for enhancement, both in terms of structure and function, within the current model. In this study, our objective is to construct a multilayered small intestinal tissue composed of an intestinal epithelium, supportive mesenchymal cells, and an extracellular matrix. We developed a multilayered small intestinal tissue by differentiating human induced pluripotent stem cells on a microfluidic device capable of replicating interstitial flow. Under the interstitial flow exposure, a three-dimensional villus-like epithelium and mature intestinal epithelial cells, including polarized enterocytes or goblet cells, were observed in the small intestine tissue-on-a-chips. Further analysis revealed that intestinal fibroblasts and collagen fiber are localized to the basolateral side of the intestinal epithelium. Moreover, we confirmed that small intestine tissue-on-a-chips are useful for pharmaceutical and infectious disease research. Our small intestine tissue-on-a-chips not only overcome the limitations of conventional small intestine models but also offer a unique opportunity to understand the mechanisms underlying intestinal tissue development.
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