Table_10_Brainstem Organoids From Human Pluripotent Stem Cells.xlsx (17.65 kB)

Table_10_Brainstem Organoids From Human Pluripotent Stem Cells.xlsx

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posted on 26.06.2020 by Nobuyuki Eura, Takeshi K. Matsui, Joachim Luginbühl, Masaya Matsubayashi, Hitoki Nanaura, Tomo Shiota, Kaoru Kinugawa, Naohiko Iguchi, Takao Kiriyama, Canbin Zheng, Tsukasa Kouno, Yan Jun Lan, Pornparn Kongpracha, Pattama Wiriyasermkul, Yoshihiko M. Sakaguchi, Riko Nagata, Tomoya Komeda, Naritaka Morikawa, Fumika Kitayoshi, Miyong Jong, Shinko Kobashigawa, Mari Nakanishi, Masatoshi Hasegawa, Yasuhiko Saito, Takashi Shiromizu, Yuhei Nishimura, Takahiko Kasai, Maiko Takeda, Hiroshi Kobayashi, Yusuke Inagaki, Yasuhito Tanaka, Manabu Makinodan, Toshifumi Kishimoto, Hiroki Kuniyasu, Shushi Nagamori, Alysson R. Muotri, Jay W. Shin, Kazuma Sugie, Eiichiro Mori

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.

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