Development of a single-cell RNA sequencing method linked to spatio-temporal cellular characteristics

• Project/Area Number: 18K19399
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Osaka University
• Principal Investigator: Kasai Atsushi 大阪大学, 薬学研究科, 准教授 (40454649)
• Co-Investigator(Kenkyū-buntansha): 奥野 浩行 鹿児島大学, 医歯学域医学系, 教授 (80272417)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: シングル細胞 / トランスクリプトーム解析 / 全脳 / ストレス / 精神疾患 / トランスクリプトーム / アノテーション / 分類 / シングル細胞RNAseq / 単一細胞 / RNAシークエンス / RNA-seq / 一細胞 / シングルセル / うつ

Outline of Final Research Achievements

Drug discovery for psychiatric disorders including depression and post-traumatic stress disorder has not been successful for many years. One of the reasons for this is thought to be the problem of omics research method, which is hypothesis-based analysis of local brain regions. Here, to identify therapeutic targets for psychiatric disorders, we established a methodology combining data-driven analysis of brain-wide activation mapping with single-cell transcriptome analysis linking the spatial information. Using this methodology, we revealed the molecular characteristics of an ensemble that are important for stress response, and found new candidate therapeutic target molecules for stress-induced mental disorders.

Academic Significance and Societal Importance of the Research Achievements

最近盛んに実施されているシングル細胞RNAシークエンス法は、脳組織から神経細胞を分散させる必要があるため、遺伝子発現情報と空間情報が直接つながらず、細胞の種類や状態の大きな変化を捉える程度しかできていない。本研究によって確立した遺伝子発現情報と機能・空間情報をつなげたシングル細胞解析法は、これまで停滞してきた脳疾患の新規機序の創薬に繋がることが期待される。

Research Products

• [Journal Article] Altered Functional Connectivity of the Orbital Cortex and Striatum Associated with Catalepsy Induced by Dopamine D1 and D2 Antagonists (2021)
  • Author(s): Misaki Niu, Atsushi Kasai, Kaoru Seiriki, Misuzu Hayashida, Masato Tanuma, Rei Yokoyama, Yumi Hirato, Hitoshi Hashimoto
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 44 Issue: 3 Pages: 442-447
  • DOI: 10.1248/bpb.b20-01006
  • NAID: 130007993460
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2021-03-01
  • Peer Reviewed / Open Access
• [Journal Article] Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain (2020)
  • Author(s): Masato Tanuma, Atsushi Kasai, Kazuki Bando, Naoyuki Kotoku, Kazuo Harada, Masafumi Minoshima, Kosuke Higashino, Atsushi Kimishima, Masayoshi Arai, Yukio Ago, Kaoru Seiriki, Kazuya Kikuchi, Satoshi Kawata, Katsumasa Fujita, Hitoshi Hashimoto
  • Journal Title: JCI Insight Volume: 5 Issue: 6
  • DOI: 10.1172/jci.insight.133348
  • Peer Reviewed / Open Access
• [Journal Article] Whole-brain block-face serial microscopy tomography at subcellular resolution using FAST. (2019)
  • Author(s): Seiriki K, Kasai A, Nakazawa T, Niu M, Naka Y, Tanuma M, Igarashi H, Yamaura K, Hayata-Takano A, Ago Y, Hashimoto H.
  • Journal Title: Nat Protoc. Volume: 印刷中 Issue: 5 Pages: 1509-1529
  • DOI: 10.1038/s41596-019-0148-4
  • Peer Reviewed / Open Access
• [Presentation] 全脳活動マッピングを用いた情動行動制御機構の解明 (2019)
  • Author(s): 笠井淳司、橋本均
  • Organizer: 生体機能と創薬シンポジウム2019
• [Presentation] 単一細胞 RNA seq によるストレス応答性神経細胞の特性解析 (2019)
  • Author(s): Tanuma M et al
  • Organizer: 第92回日本薬理学会年会
• [Remarks] 大阪大学大学院薬学研究科 神経薬理学分野 ホームページ
  • URL: http://molpharm.umin.jp/