Authors and Affiliations

Authors and Affiliations

Kwang Bo Jung^1,2, Hana Lee^1,2, Ye Seul Son^1,2, Mi-Ok Lee¹, Young-Dae Kim¹, Soo Jin Oh³, Ohman Kwon¹, Sunwha Cho¹, Hyun-Soo Cho^1,2, Dae-Soo Kim^1,2, Jung-Hwa Oh⁴, Matthias Zilbauer⁵, Jeong-Ki Min^1,2, Cho-Rok Jung^1,2,*, Janghwan Kim^1,2,* & Mi-Young Son<sup>1,2,*

1</sup> Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea. ² KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea. ³Asan Institute for Life Sciences, Asan Medical Center & Department of Convergence medicine, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea. ⁴ Korea Institute of Toxicology, Daejeon 34114, Republic of Korea. ⁵Department of Paediatric Gastroenterology, Hepatology and Nutrition, Cambridge University Hospitals, Addenbrooke’s, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK

^*Correspondence to Cho-Rok Jung or Janghwan Kim or Mi-Young Son

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.