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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3824

Title: Brainstem Organoids From Human Pluripotent Stem Cells.
Other Titles: ヒト多能性幹細胞を用いた脳幹オルガノイドの開発
Authors: Eura, Nobuyuki
Matsui, Takeshi K
Luginbühl, Joachim
Matsubayashi, Masaya
Nanaura, Hitoki
Shiota, Tomo
Kinugawa, Kaoru
Iguchi, Naohiko
Kiriyama, Takao
Zheng, Canbin
Kouno, Tsukasa
Lan, Yan Jun
Kongpracha, Pornparn
Wiriyasermkul, Pattama
Sakaguchi, Yoshihiko M
Nagata, Riko
Komeda, Tomoya
Morikawa, Naritaka
Kitayoshi, Fumika
Jong, Miyong
Kobashigawa, Shinko
Nakanishi, Mari
Hasegawa, Masatoshi
Saito, Yasuhiko
Shiromizu, Takashi
Nishimura, Yuhei
Kasai, Takahiko
Takeda, Maiko
Kobayashi, Hiroshi
Inagaki, Yusuke
Tanaka, Yasuhito
Makinodan, Manabu
Kishimoto, Toshifumi
Kuniyasu, Hiroki
Nagamori, Shushi
Muotri, Alysson R
Shin, Jay W
Sugie, Kazuma
Mori, Eiichiro
Keywords: brain organoids
brainstem
neural crest
midbrain
dopaminergic neurons
human pluripotent stem cells
melanocyte
Issue Date: 26-Jun-2020
Publisher: Frontiers Media
Citation: Frontiers in neuroscience Vol.14 Article No.538 (2020 Jun)
Abstract: The brainstem is a posterior region of the brain, composed of three parts, midbrain, pons, and medulla oblongata. It is critical in controlling heartbeat, blood pressure, and respiration, all of which are life-sustaining functions, and therefore, damages to or disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate the course of human brain development and are expected to be useful for medical research on central nervous system disorders. However, existing organoid models are limited in the extent hPSCs recapitulate human brain development and hence are not able to fully elucidate the diseases affecting various components of the brain such as brainstem. Here, we developed a method to generate human brainstem organoids (hBSOs), containing midbrain/hindbrain progenitors, noradrenergic and cholinergic neurons, dopaminergic neurons, and neural crest lineage cells. Single-cell RNA sequence (scRNA-seq) analysis, together with evidence from proteomics and electrophysiology, revealed that the cellular population in these organoids was similar to that of the human brainstem, which raises the possibility of making use of hBSOs in investigating central nervous system disorders affecting brainstem and in efficient drug screenings.
Description: 博士(医学)・乙第1479号・令和2年12月24日
Copyright © 2020 Eura, Matsui, Luginbühl, Matsubayashi, Nanaura, Shiota, Kinugawa, Iguchi, Kiriyama, Zheng, Kouno, Lan, Kongpracha, Wiriyasermkul, Sakaguchi, Nagata, Komeda, Morikawa, Kitayoshi, Jong, Kobashigawa, Nakanishi, Hasegawa, Saito, Shiromizu, Nishimura, Kasai, Takeda, Kobayashi, Inagaki, Tanaka, Makinodan, Kishimoto, Kuniyasu, Nagamori, Muotri, Shin, Sugie and Mori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
URI: http://hdl.handle.net/10564/3824
ISSN: 1662453X
DOI: https://doi.org/10.3389/fnins.2020.00538
Academic Degrees and number: 24601B1479
Degree-granting date: 2020-12-24
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2020年度

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