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Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids
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Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids
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Journal Article
Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids
2018
Overview
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.
Human pluripotent stem cell-derived intestinal organoids (hIOs) are a useful model with which to study intestinal development and disease, but they require in vivo maturation to resemble adult tissue. Here, the authors show that T lymphocyte-derived IL-2 induces hIO maturation in vitro through the activation of STAT3.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/106
/ 38
/ 38/61
/ 38/77
/ 38/91
/ 82/51
/ 82/80
/ Cell Differentiation - drug effects
/ Humanities and Social Sciences
/ Humans
/ Interleukin-2 - pharmacology
/ Pluripotent Stem Cells - cytology
/ Science
/ Signal Transduction - drug effects
/ STAT3 Transcription Factor - metabolism
/ Villus
