Cited by 560Cancer Cells and MetastasisPluripotent Stem Cells ResearchDigestive system and related health

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Human Intestinal Organoids Maintain Self-Renewal Capacity and Cellular Diversity in Niche-Inspired Culture Condition

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Fujii, Masayuki, Matano, Mami, Toshimitsu, Kohta, Takano, Ai, Mikami, Yohei, Nishikori, Shingo, Sugimoto, Shinya, Sato, Toshiro·2018·Cell Stem Cell

DOI 10.1016/j.stem.2018.11.016

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Abstract

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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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: Fujii, Masayuki
Matano, Mami
Takano, Ai
Mikami, Yohei
Nishikori, Shingo
Sugimoto, Shinya
Sato, Toshiro
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
DOI: 10.1016/j.stem.2018.11.016
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
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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Human Intestinal Organoids Maintain Self-Renewal Capacity and Cellular Diversity in Niche-Inspired Culture Condition

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