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Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids

Author

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  • Kwang Bo Jung

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Hana Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Ye Seul Son

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Mi-Ok Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Young-Dae Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Soo Jin Oh

    (University of Ulsan)

  • Ohman Kwon

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Sunwha Cho

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Hyun-Soo Cho

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Dae-Soo Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Jung-Hwa Oh

    (Korea Institute of Toxicology)

  • Matthias Zilbauer

    (Cambridge Biomedical Campus)

  • Jeong-Ki Min

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Cho-Rok Jung

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Janghwan Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Mi-Young Son

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

Abstract

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.

Suggested Citation

  • Kwang Bo Jung & Hana Lee & Ye Seul Son & Mi-Ok Lee & Young-Dae Kim & Soo Jin Oh & Ohman Kwon & Sunwha Cho & Hyun-Soo Cho & Dae-Soo Kim & Jung-Hwa Oh & Matthias Zilbauer & Jeong-Ki Min & Cho-Rok Jung &, 2018. "Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05450-8
    DOI: 10.1038/s41467-018-05450-8
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    Cited by:

    1. Eun-Jung Kang & Jae-Hoon Kim & Young Eun Kim & Hana Lee & Kwang Bo Jung & Dong-Ho Chang & Youngjin Lee & Shinhye Park & Eun-Young Lee & Eun-Ji Lee & Ho Bum Kang & Moon-Young Rhyoo & Seungwoo Seo & Soh, 2024. "The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Ohman Kwon & Hana Lee & Jaeeun Jung & Ye Seul Son & Sojeong Jeon & Won Dong Yoo & Naeun Son & Kwang Bo Jung & Eunho Choi & In-Chul Lee & Hyung-Jun Kwon & Chuna Kim & Mi-Ok Lee & Hyun-Soo Cho & Dae Soo, 2024. "Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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