@article{2f33bccc1d5c4ec7b1b483d49980457c,
title = "Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells",
abstract = "The pituitary is a major hormone center that secretes systemic hormones responding to hypothalamus-derived-releasing hormones. Previously, we reported the independent pituitary induction and hypothalamic differentiation of human embryonic stem cells (ESCs). Here, a functional hypothalamic-pituitary unit is generated using human induced pluripotent stem (iPS) cells in vitro. The adrenocorticotropic hormone (ACTH) secretion capacity of the induced pituitary reached a comparable level to that of adult mouse pituitary because of the simultaneous maturation with hypothalamic neurons within the same aggregates. Corticotropin-releasing hormone (CRH) from the hypothalamic area regulates ACTH cells similarly to our hypothalamic-pituitary axis. Our induced hypothalamic-pituitary units respond to environmental hypoglycemic condition in vitro, which mimics a life-threatening situation in vivo, through the CRH-ACTH pathway, and succeed in increasing ACTH secretion. Thus, we generated powerful hybrid organoids by recapitulating hypothalamic-pituitary development, showing autonomous maturation on the basis of interactions between developing tissues.",
author = "Takatoshi Kasai and Hidetaka Suga and Mayu Sakakibara and Chikafumi Ozone and Ryusaku Matsumoto and Mayuko Kano and Kazuki Mitsumoto and Koichiro Ogawa and Yu Kodani and Hiroshi Nagasaki and Naoko Inoshita and Mariko Sugiyama and Takeshi Onoue and Taku Tsunekawa and Yoshihiro Ito and Hiroshi Takagi and Daisuke Hagiwara and Shintaro Iwama and Motomitsu Goto and Ryoichi Banno and Jun Takahashi and Hiroshi Arima",
note = "Funding Information: We are grateful to Takeshi Nigawara for the kind gift of the CRH-R1 antibody; Saishu Yoshida and Yukio Kato for technical guidance regarding rat pituitary primary culture; Jun Arita and Akira Shimatsu for instructions in the CIBA method; Masanori Suzuki for technical assistance regarding electron microscopy; Yasumasa Iwasaki, Yutaka Oki, Yutaka Takahashi, and Koji Takano for general advice; Tomiko Yamada, Akane Yasui, and Akiko Tsuzuki for technical support; and all members of the Arima laboratory for valuable discussions. We also thank Mitchell Arico from Edanz Group ( https://www.edanzediting.com/ac ) for editing a draft of this manuscript. This work was supported by grants from the Project for Technological Development (H.S.) of the Research Center Network for Realization of Regenerative Medicine (RCNRRM) and funded by the Japan Agency for Medical Research and Development (AMED), the Acceleration Program for Intractable Diseases Research Utilizing Disease-Specific iPS Cells (H.S.) of RCNRRM funded by AMED , grants-in-aid for scientific research (H.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), and Nagoya University Hospital Funding for Clinical Research (H.S.). Funding Information: We are grateful to Takeshi Nigawara for the kind gift of the CRH-R1 antibody; Saishu Yoshida and Yukio Kato for technical guidance regarding rat pituitary primary culture; Jun Arita and Akira Shimatsu for instructions in the CIBA method; Masanori Suzuki for technical assistance regarding electron microscopy; Yasumasa Iwasaki, Yutaka Oki, Yutaka Takahashi, and Koji Takano for general advice; Tomiko Yamada, Akane Yasui, and Akiko Tsuzuki for technical support; and all members of the Arima laboratory for valuable discussions. We also thank Mitchell Arico from Edanz Group (https://www.edanzediting.com/ac) for editing a draft of this manuscript. This work was supported by grants from the Project for Technological Development (H.S.) of the Research Center Network for Realization of Regenerative Medicine (RCNRRM) and funded by the Japan Agency for Medical Research and Development (AMED), the Acceleration Program for Intractable Diseases Research Utilizing Disease-Specific iPS Cells (H.S.) of RCNRRM funded by AMED, grants-in-aid for scientific research (H.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), and Nagoya University Hospital Funding for Clinical Research (H.S.). T.K. H.S. C.O. R.M. and H.A. designed the study and wrote the manuscript. T.K. H.S. and M. Sakakibara performed the experiments with technical assistance and advice from M.K. K.M. K.O. Y.K. H.N. N.I. M. Sugiyama, T.O. T.T. Y.I. H.T. D.H. S.I. M.G. R.B. and J.T. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2020",
month = jan,
day = "7",
doi = "10.1016/j.celrep.2019.12.009",
language = "English",
volume = "30",
pages = "18--24.e5",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}