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Human Intestinal Organoids Maintain Self-Renewal Capacity and Cellular Diversity in Niche-Inspired Culture Condition
Open accessAbstract
Cellular diversity that shapes tissue architecture and function is governed by multiple niche signals. Nonetheless, maintaining cellular diversity in human intestinal organoids has been challenging. Based on niche ligands present in the natural stem cell milieu, we establish a refined organoid culture condition for intestinal epithelia that allows human intestinal organoids to concurrently undergo multi-differentiation and self-renewal. High-throughput screening reveals that the combination of insulin-like growth factor 1 (IGF-1) and fibroblast growth factor 2 (FGF-2) enhances the clonogenic capacity and CRISPR-genome engineering efficiency of human intestinal stem cells. The combination equally enables long-term culture of a range of intestinal organoids, including rat small intestinal organoids. Droplet-based single-cell RNA sequencing further illustrates the conservation of the native cellular diversity in human small intestinal organoids cultured with the refined condition. The modified culture protocol outperforms the conventional method and offers a viable strategy for modeling human intestinal tissues and diseases in an in vivo relevant context.
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“Classical crypt-villus-like architecture is regarded as an important symbol of the successful organoid establishment, exhibiting the proper branching morphology with robust multicellular composition and location reflecting the organoids differentiation and maturation level118,119.”
From Organoids (2022) · cites this paper as [119]
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“scRNA-seq analysis of human intestinal and brain organoids used random forest classifiers to identify the cell types in their organoid cultures;73,74”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [73]
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Metadata
- Authors
- Fujii, M., Matano, M., Toshimitsu, K., Takano, A., Mikami, Y., Nishikori, S., Sugimoto, S., & Sato, T.
- Affiliations
- Keio University (JP)
- Otsuka (Japan) (JP)
- Corresponding author
- Sato, Toshiro
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 23
- Issue
- 6
- Pages
- 787-793.e6
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2904971405
- Cited by
- 558
- References
- 38
- Citations by year
- 2026: 77 · 2025: 94 · 2024: 72 · 2023: 76 · 2022: 83 · 2021: 71 · 2020: 70 · 2019: 14
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development (18cm0106206h0003)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Gastroenterology › Digestive system and related health
- Keywords
- intestinal organoids, self-renewal, cellular diversity, intestinal stem cells, insulin-like growth factor I, FGF2, clonogenicity, CRISPR gene editing, small intestinal organoids, single-cell RNA sequencing, tissue engineering
- MeSH terms
- Cell Self Renewal, Animals, Cells, Cultured, Humans, Intestines, Male, Organoids, Rats, Inbred Lew, Cell Culture Techniques, Rats, Stem Cell Niche
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