title: Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes.
abstract: The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P) and dorsoventral (D-V) axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Kent
authors.initials: K
authors.lastname: Imaizumi
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Sone
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Ibata
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Fujimori
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyoku, Tokyo 113-8421, Japan. Electronic address: awado@juntendo.ac.jp.
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: hidokano@a2.keio.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques; D002460:Cell Line; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D060449:Wnt Signaling Pathway
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human