Brainstem organoids from human pluripotent stem cells contain neural crest population
Brainstem organoids from human pluripotent stem cells contain neural crest population
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DOI：
10.1101/829275
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
N. Eura;Takeshi K. Matsui;J. Luginbühl;Masaya Matsubayashi;H. Nanaura;T. Shiota;K. Kinugawa;N. Iguchi;T. Kiriyama;Canbin Zheng;Tsukasa Kouno;Y. Lan;P. Kongpracha;Pattama Wiriyasermkul;Yoshihiko M. Sakaguchi;Riko Nagata;Tomoya Komeda;Naritaka Morikawa;Fumika Kitayoshi;Miyong Jong;Shinko Kobashigawa;Mari Nakanishi;M. Hasegawa;Yasuhiko Saito;Takashi Shiromizu;Y. Nishimura;T. Kasai;Maiko Takeda;Hiroshi Kobayashi;Y. Inagaki;Yasuhito Tanaka;M. Makinodan;T. Kishimoto;H. Kuniyasu;S. Nagamori;A. Muotri;Jay W. Shin;K. Sugie;Eiichiro Mori
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文献类型：
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作者：
N. Eura;Takeshi K. Matsui;J. Luginbühl;Masaya Matsubayashi;H. Nanaura;T. Shiota;K. Kinugawa;N. Iguchi;T. Kiriyama;Canbin Zheng;Tsukasa Kouno;Y. Lan;P. Kongpracha;Pattama Wiriyasermkul;Yoshihiko M. Sakaguchi;Riko Nagata;Tomoya Komeda;Naritaka Morikawa;Fumika Kitayoshi;Miyong Jong;Shinko Kobashigawa;Mari Nakanishi;M. Hasegawa;Yasuhiko Saito;Takashi Shiromizu;Y. Nishimura;T. Kasai;Maiko Takeda;Hiroshi Kobayashi;Y. Inagaki;Yasuhito Tanaka;M. Makinodan;T. Kishimoto;H. Kuniyasu;S. Nagamori;A. Muotri;Jay W. Shin;K. Sugie;Eiichiro Mori
脑干控制心跳、血压和呼吸，这些都是维持生命的功能，因此，脑干的紊乱可能是致命的。来源于人类多能干细胞的脑类器官概括了人类大脑发育的过程，预计可用于中枢神经系统疾病的医学研究。然而，现有的类器官模型存在局限性，阻碍了对影响大脑特定成分的疾病的阐明。在这里，我们开发了一种方法来产生人脑干类器官（hBSO），包含神经嵴干细胞以及中脑/后脑祖细胞，去甲肾上腺素能和胆碱能神经元，多巴胺能神经元，通过特定的电生理特征证明。单细胞RNA序列分析，以及蛋白质组学和电生理学，揭示了这些类器官中的细胞群体与人类脑干和神经嵴的细胞群体相似，这提高了利用hBSO进行移植，有效药物筛选和神经嵴疾病建模的可能性。
The brainstem controls heartbeat, blood pressure and respiration, which are life-sustaining functions, therefore, disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells 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 have limitations, hampering the elucidation of diseases affecting specific components of the brain. Here, we developed a method to generate human brainstem organoids (hBSOs), containing neural crest stem cells as well as midbrain/hindbrain progenitors, noradrenergic and cholinergic neurons, and dopaminergic neurons, demonstrated by specific electrophysiological signatures. Single-cell RNA sequence analysis, together with proteomics and electrophysiology, revealed that the cellular population in these organoids was similar to that of the human brainstem and neural crest, which raises the possibility of making use of hBSOs in grafting for transplantation, efficient drug screenings and modeling the neural crest diseases.