Identification of genes and key molecular pathways determining cluster/hub cells and analysis of their association with human diseases
| Project Area | Morphological features and gene expression patterns underlying hub neurons |
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| Project/Area Number |
20H05777
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| Research Category |
Grant-in-Aid for Transformative Research Areas (B)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (III)
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Takata Atsushi 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (90643693)
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| Project Period (FY) |
2020-10-02 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥43,550,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥10,050,000)
Fiscal Year 2022: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2021: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2020: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
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| Keywords | マルチモーダル一細胞 / RNAシーケンス / 精神神経疾患 / 遺伝統計 / 機械学習 |
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| Outline of Research at the Start |
本研究領域は、神経ネットワーク内で機能的クラスタを形成する細胞群（クラスタ細胞）と、クラスタ内ネットワークで中心となる細胞（ハブ細胞）のダイナミズムを決定づける剛軟因子、すなわち神経細胞形態（剛）と遺伝子発現変動（軟）の追究を目標とする。本研究班では、一細胞神経活動記録とRNA-seqデータを突合させたマルチモーダル一細胞解析の手法開発を領域内連携で進め、またそのデータの多角的バイオインフォマティクス解析を行う。これらの解析によって、クラスタ/ハブ細胞を決定づける「軟」因子を遺伝子レベル、分子経路レベルで特定し、また疾患等における役割を明らかにすることを目指す。
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| Outline of Final Research Achievements |
In this project, we developed a prototype of an experimental and analytical pipeline to rapidly identify clusters/hub cells from wide field-of-view neural activity recording data, artificially label these cells, and analyze their transcriptomic profiles using single-cell RNA-seq, by closely collaborating with the Murayama and Takeda groups. Our Planned Research group established an informatics pipeline for single-cell RNA-seq data to quantify expression levels of genes including artificially expressed genes for labeling, identify genes characterizing the cell population of interest, and statistically evaluate the overlap between these genes and disease-associated genes or genomic loci. We also applied this pipeline to single-cell RNA-seq data from the brain of an animal model of neuropsychiatric disorder and identified cell types with prominent disease-associated alterations in the transcriptomic profile.
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| Academic Significance and Societal Importance of the Research Achievements |
本領域では、神経活動データ・一細胞RNA-seqデータ・神経形態データ等を、神経科学者・数理情報学者・バイオインフォマティストの密な連携を通じて統合的に解析し、その対応関係等を明らかにするためのパイプライン開発を進めた。この枠組みは、本領域で主要対象としたハブ/クラスタ細胞のみならず、あらゆるタイプの関心細胞集団を対象としたマルチモーダル研究に応用可能であるため、学術的意義が高いものと考える（ただし、さらなる性能向上の必要性があるとも認識している）。また、こういった解析手法を用いたヒト脳疾患の研究は、病態理解に新たな洞察をもたらし治療・予防法開発にも繋がりうるという点で社会的意義を有する。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants.2022
Author(s)
Hamanaka K, Miyake N, Mizuguchi T, Miyatake S, Uchiyama Y, Tsuchida N, Sekiguchi F, Mitsuhashi S, Tsurusaki Y, Nakashima M, Saitsu H, Yamada K, Sakamoto M, Fukuda H, Ohori S, Saida K, Itai T, Azuma Y, Koshimizu E, Fujita A, Erturk B, Hiraki Y, Ch'ng GS, Kato M, Okamoto N, Takata A, Matsumoto N.
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Journal Title
Genome Med
Volume: 14
Issue: 1
Pages: 40-40
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Complete sequencing of expanded SAMD12 repeats by long-read sequencing with Cas9-mediated enrichment.2021
Author(s)
Mizuguchi T, Toyota T, Miyatake S, Mitsuhashi S, Doi H, Kudo Y, Kishida H, Hayashi N, Tusburaya RS, Kinoshita M, Fukuyama T, Fukuda H, Koshimizu E, Tsuchida N, Uchiyama Y, Fujita A, Takata A, Miyake N, Kato M, Tanaka F, Adachi H, Matsumoto N.
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Journal Title
Brain
Volume: 144
Issue: 4
Pages: 1103-1117
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H(+)-ATPases is essential for brain development in humans and mice2021
Author(s)
Aoto K, Kato M, Akita T, Nakashima M, Mutoh H, Akasaka N, Tohyama J, Nomura Y, Hoshino K, Ago Y, Tanaka R, Epstein O, Ben-Haim R, Heyman E, Miyazaki T, Belal H, Takabayashi S, Ohba C, Takata A, Mizuguchi T, Miyatake S, Miyake N, Fukuda A, Matsumoto N and Saitsu H
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Journal Title
Nat Commun
Volume: 12
Issue: 1
Pages: 2107-2107
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hemizygous FLNA variant in West syndrome without periventricular nodular heterotopia2020
Author(s)
Hiromoto Y, Azuma Y, Suzuki Y, Hoshina M, Uchiyama Y, Mitsuhashi S, Miyatake S, Mizuguchi T, Takata A, Miyake N, Kato M, Matsumoto N.
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Journal Title
Hum Genome Var
Volume: 7
Issue: 1
Pages: 43-43
DOI
Related Report
Peer Reviewed / Open Access
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