AUTHOR=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 TITLE=Brainstem Organoids From Human Pluripotent Stem Cells JOURNAL=Frontiers in Neuroscience VOLUME=14 YEAR=2020 URL=https://www.frontiersin.org/journals/neuroscience/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.