Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells

Takatoshi Kasai, Hidetaka Suga, Mayu Sakakibara, Chikafumi Ozone, Ryusaku Matsumoto, Mayuko Kano, Kazuki Mitsumoto, Koichiro Ogawa, Yu Kodani, Hiroshi Nagasaki, Naoko Inoshita, Mariko Sugiyama, Takeshi Onoue, Taku Tsunekawa, Yoshihiro Ito, Hiroshi Takagi, Daisuke Hagiwara, Shintaro Iwama, Motomitsu Goto, Ryoichi BannoJun Takahashi, Hiroshi Arima

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)18-24.e5
JournalCell Reports
Volume30
Issue number1
DOIs
Publication statusPublished - 07-01-2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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