@ARTICLE{10.3389/fnins.2020.00538, AUTHOR={Eura, Nobuyuki and Matsui, Takeshi K. and Luginbühl, Joachim and Matsubayashi, Masaya and Nanaura, Hitoki and Shiota, Tomo and Kinugawa, Kaoru and Iguchi, Naohiko and Kiriyama, Takao and Zheng, Canbin and Kouno, Tsukasa and Lan, Yan Jun and Kongpracha, Pornparn and Wiriyasermkul, Pattama and Sakaguchi, Yoshihiko M. and Nagata, Riko and Komeda, Tomoya and Morikawa, Naritaka and Kitayoshi, Fumika and Jong, Miyong and Kobashigawa, Shinko and Nakanishi, Mari and Hasegawa, Masatoshi and Saito, Yasuhiko and Shiromizu, Takashi and Nishimura, Yuhei and Kasai, Takahiko and Takeda, Maiko and Kobayashi, Hiroshi and Inagaki, Yusuke and Tanaka, Yasuhito and Makinodan, Manabu and Kishimoto, Toshifumi and Kuniyasu, Hiroki and Nagamori, Shushi and Muotri, Alysson R. and Shin, Jay W. and Sugie, Kazuma and Mori, Eiichiro}, TITLE={Brainstem Organoids From Human Pluripotent Stem Cells}, JOURNAL={Frontiers in Neuroscience}, VOLUME={14}, YEAR={2020}, URL={https://www.frontiersin.org/articles/10.3389/fnins.2020.00538}, DOI={10.3389/fnins.2020.00538}, ISSN={1662-453X}, 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.} }