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 Banno; Jun Takahashi; Hiroshi Arima

doi:10.1016/j.celrep.2019.12.009

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 Banno

Jun Takahashi, Hiroshi Arima

Research output: Contribution to journal › Article › peer-review

88 Citations (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 language	English
Pages (from-to)	18-24.e5
Journal	Cell Reports
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2019.12.009
Publication status	Published - 07-01-2020
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.celrep.2019.12.009

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Kasai, T., Suga, H., Sakakibara, M., Ozone, C., Matsumoto, R., Kano, M., Mitsumoto, K., Ogawa, K., Kodani, Y., Nagasaki, H., Inoshita, N., Sugiyama, M., Onoue, T., Tsunekawa, T., Ito, Y., Takagi, H., Hagiwara, D., Iwama, S., Goto, M., ... Arima, H. (2020). Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells. Cell Reports, 30(1), 18-24.e5. https://doi.org/10.1016/j.celrep.2019.12.009

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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.",

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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",

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day = "7",

doi = "10.1016/j.celrep.2019.12.009",

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Kasai, T, Suga, H, Sakakibara, M, Ozone, C, Matsumoto, R, Kano, M, Mitsumoto, K, Ogawa, K, Kodani, Y , Nagasaki, H, Inoshita, N, Sugiyama, M, Onoue, T, Tsunekawa, T, Ito, Y, Takagi, H, Hagiwara, D, Iwama, S, Goto, M, Banno, R, Takahashi, J & Arima, H 2020, 'Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells', Cell Reports, vol. 30, no. 1, pp. 18-24.e5. https://doi.org/10.1016/j.celrep.2019.12.009

TY - JOUR

T1 - Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells

AU - Kasai, Takatoshi

AU - Suga, Hidetaka

AU - Sakakibara, Mayu

AU - Ozone, Chikafumi

AU - Matsumoto, Ryusaku

AU - Kano, Mayuko

AU - Mitsumoto, Kazuki

AU - Ogawa, Koichiro

AU - Kodani, Yu

AU - Nagasaki, Hiroshi

AU - Inoshita, Naoko

AU - Sugiyama, Mariko

AU - Onoue, Takeshi

AU - Tsunekawa, Taku

AU - Ito, Yoshihiro

AU - Takagi, Hiroshi

AU - Hagiwara, Daisuke

AU - Iwama, Shintaro

AU - Goto, Motomitsu

AU - Banno, Ryoichi

AU - Takahashi, Jun

AU - Arima, Hiroshi

PY - 2020/1/7

Y1 - 2020/1/7

N2 - 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.

AB - 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.

KW - 3D culture

KW - functional unit

KW - human iPS cells

KW - hypothalamus

KW - interaction

KW - organoid

KW - pituitary

KW - self-organization

UR - https://www.scopus.com/pages/publications/85077306864

UR - https://www.scopus.com/pages/publications/85077306864#tab=citedBy

U2 - 10.1016/j.celrep.2019.12.009

DO - 10.1016/j.celrep.2019.12.009

M3 - Article

C2 - 31914385

AN - SCOPUS:85077306864

SN - 2211-1247

VL - 30

SP - 18-24.e5

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

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

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