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ヒト多能性幹細胞を用いた脳幹オルガノイドの開発
Authors
Nobuyuki Eura
Masatoshi Hasegawa
+37 more
Naohiko Iguchi
Yusuke Inagaki
Miyong Jong
Takahiko Kasai
Kaoru Kinugawa
Takao Kiriyama
Toshifumi Kishimoto
Fumika Kitayoshi
Shinko Kobashigawa
Hiroshi Kobayashi
Tomoya Komeda
Pornparn Kongpracha
Tsukasa Kouno
Hiroki Kuniyasu
Yan Jun Lan
Joachim Luginbühl
Manabu Makinodan
Masaya Matsubayashi
Takeshi K Matsui
Eiichiro Mori
Naritaka Morikawa
Alysson R Muotri
Shushi Nagamori
Riko Nagata
Mari Nakanishi
Hitoki Nanaura
Yuhei Nishimura
Yasuhiko Saito
Yoshihiko M Sakaguchi
Jay W Shin
Tomo Shiota
Takashi Shiromizu
Kazuma Sugie
Maiko Takeda
Yasuhito Tanaka
Pattama Wiriyasermkul
Canbin Zheng
Publication date
24 December 2020
Publisher
'Frontiers Media SA'
Doi
Cite
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.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
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Last time updated on 24/01/2021