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Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells

Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development o...

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Autores principales: Ozone, Chikafumi, Suga, Hidetaka, Eiraku, Mototsugu, Kadoshima, Taisuke, Yonemura, Shigenobu, Takata, Nozomu, Oiso, Yutaka, Tsuji, Takashi, Sasai, Yoshiki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735598/
https://www.ncbi.nlm.nih.gov/pubmed/26762480
http://dx.doi.org/10.1038/ncomms10351
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author Ozone, Chikafumi
Suga, Hidetaka
Eiraku, Mototsugu
Kadoshima, Taisuke
Yonemura, Shigenobu
Takata, Nozomu
Oiso, Yutaka
Tsuji, Takashi
Sasai, Yoshiki
author_facet Ozone, Chikafumi
Suga, Hidetaka
Eiraku, Mototsugu
Kadoshima, Taisuke
Yonemura, Shigenobu
Takata, Nozomu
Oiso, Yutaka
Tsuji, Takashi
Sasai, Yoshiki
author_sort Ozone, Chikafumi
collection PubMed
description Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine.
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spelling pubmed-47355982016-03-04 Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells Ozone, Chikafumi Suga, Hidetaka Eiraku, Mototsugu Kadoshima, Taisuke Yonemura, Shigenobu Takata, Nozomu Oiso, Yutaka Tsuji, Takashi Sasai, Yoshiki Nat Commun Article Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine. Nature Publishing Group 2016-01-14 /pmc/articles/PMC4735598/ /pubmed/26762480 http://dx.doi.org/10.1038/ncomms10351 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ozone, Chikafumi
Suga, Hidetaka
Eiraku, Mototsugu
Kadoshima, Taisuke
Yonemura, Shigenobu
Takata, Nozomu
Oiso, Yutaka
Tsuji, Takashi
Sasai, Yoshiki
Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
title Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
title_full Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
title_fullStr Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
title_full_unstemmed Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
title_short Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
title_sort functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735598/
https://www.ncbi.nlm.nih.gov/pubmed/26762480
http://dx.doi.org/10.1038/ncomms10351
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