Frontiers in Neuroscience (Jun 2020)
Brainstem Organoids From Human Pluripotent Stem Cells
- Nobuyuki Eura,
- Takeshi K. Matsui,
- Takeshi K. Matsui,
- Joachim Luginbühl,
- Masaya Matsubayashi,
- Hitoki Nanaura,
- 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,
- Alysson R. Muotri,
- Jay W. Shin,
- Kazuma Sugie,
- Eiichiro Mori
Affiliations
- Nobuyuki Eura
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Takeshi K. Matsui
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Takeshi K. Matsui
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Joachim Luginbühl
- Laboratory for Advanced Genomics Circuit, RIKEN Center for Integrative Medical Sciences, Yokohama,Japan
- Masaya Matsubayashi
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Hitoki Nanaura
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Hitoki Nanaura
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Tomo Shiota
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Kaoru Kinugawa
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Naohiko Iguchi
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Takao Kiriyama
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Canbin Zheng
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, United States
- Tsukasa Kouno
- Laboratory for Advanced Genomics Circuit, RIKEN Center for Integrative Medical Sciences, Yokohama,Japan
- Yan Jun Lan
- Laboratory for Advanced Genomics Circuit, RIKEN Center for Integrative Medical Sciences, Yokohama,Japan
- Pornparn Kongpracha
- Laboratory of Biomolecular Dynamics, Department of Collaborative Research, Nara Medical University, Kashihara, Japan
- Pattama Wiriyasermkul
- Laboratory of Biomolecular Dynamics, Department of Collaborative Research, Nara Medical University, Kashihara, Japan
- Yoshihiko M. Sakaguchi
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Riko Nagata
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Tomoya Komeda
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Naritaka Morikawa
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Fumika Kitayoshi
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Miyong Jong
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Shinko Kobashigawa
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Mari Nakanishi
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- Masatoshi Hasegawa
- Department of Radiation Oncology, Nara Medical University, Kashihara, Japan
- Yasuhiko Saito
- Department of Neurophysiology, Nara Medical University, Kashihara, Japan
- Takashi Shiromizu
- Department of Integrative Pharmacology, Graduate School of Medicine, Mie University, Tsu, Japan
- Yuhei Nishimura
- Department of Integrative Pharmacology, Graduate School of Medicine, Mie University, Tsu, Japan
- Takahiko Kasai
- Department of Laboratory Medicine and Pathology, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan
- Maiko Takeda
- Department of Laboratory Medicine and Pathology, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan
- Hiroshi Kobayashi
- 0Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan
- Yusuke Inagaki
- 1Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan
- Yasuhito Tanaka
- 1Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan
- Manabu Makinodan
- 2Department of Psychiatry, Nara Medical University, Kashihara, Japan
- Toshifumi Kishimoto
- 2Department of Psychiatry, Nara Medical University, Kashihara, Japan
- Hiroki Kuniyasu
- 3Department of Molecular Pathology, Nara Medical University, Kashihara, Japan
- Shushi Nagamori
- Laboratory of Biomolecular Dynamics, Department of Collaborative Research, Nara Medical University, Kashihara, Japan
- Alysson R. Muotri
- 4Department of Pediatrics, University of California, San Diego, San Diego, CA, United States
- Alysson R. Muotri
- 5Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, CA, United States
- Jay W. Shin
- Laboratory for Advanced Genomics Circuit, RIKEN Center for Integrative Medical Sciences, Yokohama,Japan
- Kazuma Sugie
- Department of Neurology, Nara Medical University, Kashihara, Japan
- Eiichiro Mori
- Department of Future Basic Medicine, Nara Medical University, Kashihara, Japan
- DOI
- https://doi.org/10.3389/fnins.2020.00538
- Journal volume & issue
-
Vol. 14
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.
Keywords
