Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids
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Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation.
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Functional intestinal organoids have a relatively thick mucus layer because mature goblet cells secrete mucus.
“Furtherly, functional intestinal organoids exhibit a relatively thick mucus layer due to mucus secretion from mature goblet cells122, which can be detected by Alcian blue (AB) and periodic acid-Schiff (PAS) staining123,124.”
From Organoids (2022) · cites this paper as [122]
The Results (‘hIOs matured in vitro display enhanced functionality,’ Fig. 4g; page unavailable) report mucin-secreting goblet cells and show staining for a mucous layer in the matured organoids. The Discussion identifies these as mucus-producing mature goblet cells. The paper does not establish that the layer is relatively thick, so that part of the attributed claim is unsupported. (LLM, conf=0.86)
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- Authors
- Jung, K. B., Lee, H., Son, Y. S., Lee, M.-O., Kim, Y.-D., Oh, S. J., Kwon, O., Cho, S., Cho, H.-S., Kim, D.-S., Oh, J.-H., Zilbauer, M., Min, J.-K., Jung, C.-R., Kim, J., & Son, M.-Y.
- Affiliations
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Asan Medical Center (KR)
- Korea Institute of Toxicology (KR)
- Addenbrooke's Hospital (GB)
- Corresponding author
- Kim, Young-Dae
- Jung, Cho-Rok
- Kim, Janghwan
- Son, Mi-Young
- ORCID
- Venue
- Nature Communications
- Published
- 2018-08-02
- Volume
- 9
- Issue
- 1
- Pages
- 3039-3039
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6072745
- OpenAlex
- W2883753684
- Cited by
- 125
- References
- 52
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 19 · 2023: 6 · 2022: 18 · 2021: 19 · 2020: 25 · 2019: 14 · 2018: 4
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- KRIBB Repository (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- National Research Foundation of Korea (2016R1A2B4013501)
- Korea Research Institute of Bioscience and Biotechnology (KRIBB Research Initiative Program)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- intestinal organoids, pluripotent stem cells, interleukin-2, STAT3 signaling, organoid maturation, T cells, co-culture, intestinal epithelium, intestinal development
- MeSH terms
- Cell Differentiation, Humans, Interleukin-2, Intestines, Organoids, T-Lymphocytes, Signal Transduction, Biomarkers, Coculture Techniques, Pluripotent Stem Cells, STAT3 Transcription Factor
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