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Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells.
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.celrep.2019.12.009 Takatoshi Kasai 1 , Hidetaka Suga 1 , Mayu Sakakibara 1 , Chikafumi Ozone 1 , Ryusaku Matsumoto 2 , Mayuko Kano 1 , Kazuki Mitsumoto 1 , Koichiro Ogawa 1 , Yu Kodani 3 , Hiroshi Nagasaki 3 , Naoko Inoshita 4 , Mariko Sugiyama 1 , Takeshi Onoue 1 , Taku Tsunekawa 1 , Yoshihiro Ito 1 , Hiroshi Takagi 1 , Daisuke Hagiwara 1 , Shintaro Iwama 1 , Motomitsu Goto 1 , Ryoichi Banno 1 , Jun Takahashi 5 , Hiroshi Arima 1
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.celrep.2019.12.009 Takatoshi Kasai 1 , Hidetaka Suga 1 , Mayu Sakakibara 1 , Chikafumi Ozone 1 , Ryusaku Matsumoto 2 , Mayuko Kano 1 , Kazuki Mitsumoto 1 , Koichiro Ogawa 1 , Yu Kodani 3 , Hiroshi Nagasaki 3 , Naoko Inoshita 4 , Mariko Sugiyama 1 , Takeshi Onoue 1 , Taku Tsunekawa 1 , Yoshihiro Ito 1 , Hiroshi Takagi 1 , Daisuke Hagiwara 1 , Shintaro Iwama 1 , Motomitsu Goto 1 , Ryoichi Banno 1 , Jun Takahashi 5 , Hiroshi Arima 1
Affiliation
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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.
中文翻译：
下丘脑对垂体功能的贡献是使用3D培养的人iPS细胞体外概括的。
垂体是主要的激素中心，其分泌响应下丘脑衍生的释放激素的全身激素。以前，我们报道了人类胚胎干细胞（ESC）的独立垂体诱导和下丘脑分化。在这里，使用人诱导的多能干（iPS）细胞在体外产生功能性下丘脑-垂体单元。诱导垂体的促肾上腺皮质激素（ACTH）分泌能力达到了成年小鼠垂体的相当水平，因为在同一聚集体中下丘脑神经元同时成熟。下丘脑区域的促肾上腺皮质激素释放激素（CRH）与我们的下丘脑-垂体轴类似地调节ACTH细胞。我们诱导的下丘脑-垂体单位在体外对环境降血糖情况有反应，通过CRH-ACTH途径模拟体内威胁生命的情况，并成功增加ACTH分泌。因此，我们通过概括下丘脑-垂体的发育，产生了强大的杂种类器官，在发育组织之间的相互作用基础上显示出自主成熟。
更新日期：2020-01-07
中文翻译：
下丘脑对垂体功能的贡献是使用3D培养的人iPS细胞体外概括的。
垂体是主要的激素中心，其分泌响应下丘脑衍生的释放激素的全身激素。以前，我们报道了人类胚胎干细胞（ESC）的独立垂体诱导和下丘脑分化。在这里，使用人诱导的多能干（iPS）细胞在体外产生功能性下丘脑-垂体单元。诱导垂体的促肾上腺皮质激素（ACTH）分泌能力达到了成年小鼠垂体的相当水平，因为在同一聚集体中下丘脑神经元同时成熟。下丘脑区域的促肾上腺皮质激素释放激素（CRH）与我们的下丘脑-垂体轴类似地调节ACTH细胞。我们诱导的下丘脑-垂体单位在体外对环境降血糖情况有反应，通过CRH-ACTH途径模拟体内威胁生命的情况，并成功增加ACTH分泌。因此，我们通过概括下丘脑-垂体的发育，产生了强大的杂种类器官，在发育组织之间的相互作用基础上显示出自主成熟。
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