Elucidation of the system constructing skeletal muscle tissue by whole-cell omics.

• Project/Area Number: 20H00456
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Ohkawa Yasuyuki 九州大学, 生体防御医学研究所, 教授 (80448430)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000); Fiscal Year 2022: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2021: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2020: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
• Keywords: 骨格筋分化 / クロマチン構造 / 単一細胞解析 / 空間オミクス

Outline of Research at the Start

全細胞オミクスによる骨格筋組織を構築するシステムの解明遺伝子発現は細胞の機能を構築、維持する根源的なシステムの一つである。生体内における遺伝子発現はクロマチン構造上で制御され、膨大な数の遺伝子が秩序だった制御を受けることで特定の形質を獲得する。本研究課題ではクロマチン構造上の遺伝子発現制御により集約化される生体構築情報を全細胞レベルで習得し、組織固有の細胞の集団の獲得と細胞間で伝達されるコミュニケーションの全貌を解き明かす。以って生命の普遍的な謎であった細胞の集合体としての組織機能の獲得を網羅的解析と高度の情報科学を融合させた解析により迫る。

Outline of Final Research Achievements

The unique ChILSeq method facilitated single-cell level epigenome data acquisition. An innovative multi-omics analysis integrated ChILSeq with a novel immunostaining method and a spatial transcriptome technique, PIC. This application in tissues allows intra-tissue epigenomic changes analysis. RNA was reverse-transcribed into dsDNA, amplified via in vitro transcription for single-cell RNA detection. Specific antibodies labeled with erasable fluorescence were used to analyze a wide variety of antibodies within the same specimen. The ongoing comprehensive data analysis aims to identify cell populations in skeletal muscle regeneration, with paper submission and patent application in progress.

Academic Significance and Societal Importance of the Research Achievements

本研究は、骨格筋再生過程における細胞集団の詳細な同定を可能にし、それにより筋肉損傷や筋萎縮症などの筋肉疾患の治療法開発に対する重要なデータとなるであろう。単一細胞レベルでのトランスクリプトーム、プロテオーム、エピゲノムデータの取得は、患者の病態理解とパーソナライズド医療の進展に資する。また、この独自のマルチオミクス解析法は生体組織のエピゲノム変化を詳細に解析可能で、がんなど他の疾患の研究にも応用可能な可能性がある。論文の公開と特許申請により、これら技術は更なる研究と開発の基盤となることが期待できる。

Research Products

• [Journal Article] Design and implementation of a hybrid cloud system for large-scale human genomic research. (2023)
  • Author(s): Masao Nagasaki, Yayoi Sekiya, Akihiro Asakura, Ryo Teraoka, Ryoko Otokozawa, Hiroki Hashimoto, Takahisa Kawaguchi, Keiichiro Fukazawa, Yuichi Inadomi, Ken T Murata, Yasuyuki Ohkawa, Izumi Yamaguchi, Takamichi Mizuhara, Katsushi Tokunaga, Yuji Sekiya, Toshihiro Hanawa, Ryo Yamada, Fumihiko Matsuda.
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• [Journal Article] STREAMING-tag system reveals spatiotemporal relationships between transcriptional regulatory factors and transcriptional activity (2022)
  • Author(s): Ohishi Hiroaki、Shimada Seiru、Uchino Satoshi、Li Jieru、Sato Yuko、Shintani Manabu、Owada Hitoshi、Ohkawa Yasuyuki、Pertsinidis Alexandros、Yamamoto Takashi、Kimura Hiroshi、Ochiai Hiroshi
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 7672-7672
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prostaglandin E2 receptor Ptger4b regulates female-specific peptidergic neurons and female sexual receptivity in medaka (2022)
  • Author(s): Fleming Thomas、Kikuchi Yukiko、Nakajo Mikoto、Tachizawa Masaya、Inazumi Tomoaki、Tsuchiya Soken、Sugimoto Yukihiko、Saito Daisuke、Suyama Mikita、Ohkawa Yasuyuki、Baba Takashi、Morohashi Ken-ichirou、Okubo Kataaki
  • Journal Title: Communications Biology Volume: 5 Issue: 1 Pages: 1215-1215
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• [Journal Article] Drosophila transcription factor NF-Y suppresses transcription of the lipase 4 gene, a key gene for lipid storage. (2022)
  • Author(s): Yasuhide Yoshioka, Keisuke Anzai, Ryosuke Kowada, Ken Hiratsuka, Teppei Hirayabu, Masashi Yasuda, Yasuyuki Ohkawa, Tetsuya Sato, Mikita Suyama, Hideki Yoshida, Masamitsu Yamaguchi.
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• [Journal Article] Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway. (2022)
  • Author(s): Miki Inoue, Takashi Baba, Fumiya Takahashi, Miho Terao, Shogo Yanai, Yuichi Shima, Daisuke Saito, Kei Sugihara, Takashi Miura, Shuji Takada, Mikita Suyama, Yasuyuki Ohkawa, Ken-Ichirou Morohashi.
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• [Journal Article] Identification of a drug-response gene in multiple myeloma through longitudinal single-cell transcriptome sequencing (2022)
  • Author(s): Masuda Toru、Haji Shojiro、Nakashima Yasuhiro、Tsuda Mariko、Kimura Daisaku、Takamatsu Akiko、Iwahashi Norifusa、Umakoshi Hironobu、Shiratsuchi Motoaki、Kikutake Chie、Suyama Mikita、Ohkawa Yasuyuki、Ogawa Yoshihiro
  • Journal Title: iScience Volume: 25 Issue: 8 Pages: 104781-104781
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• [Journal Article] Uterus-specific transcriptional regulation underlies eggshell pigment production in Japanese quail (2022)
  • Author(s): Ishishita Satoshi、Kitahara Shumpei、Takahashi Mayuko、Iwasaki Sakura、Tatsumoto Shoji、Hara Izumi、Kaneko Yoshiki、Kinoshita Keiji、Yamaguchi Katsushi、Harada Akihito、Ohmori Yasushige、Ohkawa Yasuyuki、Go Yasuhiro、Shigenobu Shuji、Matsuda Yoichi、Suzuki Takayuki
  • Journal Title: PLOS ONE Volume: 17 Issue: 3 Pages: 0265008-0265008
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  • Peer Reviewed / Open Access
• [Journal Article] Photo-isolation chemistry for high-resolution and deep spatial transcriptome with mouse tissue sections (2022)
  • Author(s): Honda Mizuki、Kimura Ryuichi、Harada Akihito、Maehara Kazumitsu、Tanaka Kaori、Ohkawa Yasuyuki、Oki Shinya
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  • Peer Reviewed / Open Access
• [Journal Article] Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation (2022)
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  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 10 Pages: 780038-780038
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  • Peer Reviewed / Open Access
• [Journal Article] Direct Conversion of Human Endothelial Cells Into Liver Cancer-Forming Cells Using Nonintegrative Episomal Vectors. (2022)
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• [Journal Article] Uhrf1 governs the proliferation and differentiation of muscle satellite cells. (2022)
  • Author(s): Sakai H, Sawada Y, Tokunaga N, Tanaka K, Nakagawa S, Sakakibara I, Ono Y, Fukada SI, Ohkawa Y, Kikugawa T, Saika T, Imai Y.
  • Journal Title: iScience. Volume: 25 Issue: 3 Pages: 103928-103928
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  • Peer Reviewed / Open Access
• [Journal Article] Live imaging of transcription sites using an elongating RNA polymerase II-specific probe. (2022)
  • Author(s): Uchino S, Ito Y, Sato Y, Handa T, Ohkawa Y, Tokunaga M, Kimura H.
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• [Journal Article] Unusual nucleosome formation and transcriptome influence by the histone H3mm18 variant (2021)
  • Author(s): Hirai Seiya、Tomimatsu Kosuke、Miyawaki-Kuwakado Atsuko、Takizawa Yoshimasa、Komatsu Tetsuro、Tachibana Taro、Fukushima Yutaro、Takeda Yasuko、Negishi Lumi、Kujirai Tomoya、Koyama Masako、Ohkawa Yasuyuki、Kurumizaka Hitoshi
  • Journal Title: Nucleic Acids Research Volume: 50 Issue: 1 Pages: 72-91
  • DOI: 10.1093/nar/gkab1137
  • Peer Reviewed / Open Access
• [Journal Article] Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load. (2021)
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  • Journal Title: Cell Stem Cell. Volume: 29 Issue: 2 Pages: 265-280
  • DOI: 10.1016/j.stem.2021.11.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recent advances in single-cell epigenomics. (2021)
  • Author(s): Harada A, Kimura H, Ohkawa Y.
  • Journal Title: Curr Opin Struct Biol. Volume: 71 Pages: 116-122
  • Peer Reviewed / Open Access
• [Journal Article] High-throughput single-cell epigenomic profiling by targeted insertion of promoters (TIP-seq). (2021)
  • Author(s): Bartlett DA, Dileep V, Handa T, Ohkawa Y, Kimura H, Henikoff S, Gilbert DM.
  • Journal Title: J Cell Biol. Volume: 220 Issue: 12
  • DOI: 10.1083/jcb.202103078
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• [Journal Article] Chromatin loading of MCM hexamers is associated with di-/tri-methylation of histone H4K20 toward S phase entry. (2021)
  • Author(s): Hayashi-Takanaka Y, Hayashi Y, Hirano Y, Miyawaki-Kuwakado A, Ohkawa Y, Obuse C, Kimura H, Haraguchi T, Hiraoka Y.
  • Journal Title: Nucleic Acids Res. Volume: 49 Issue: 21 Pages: 12152-12166
  • DOI: 10.1093/nar/gkab1068
  • Peer Reviewed / Open Access
• [Journal Article] Discriminative feature of cells characterizes cell populations of interest by a small subset of genes. (2021)
  • Author(s): Fujii T, Maehara K, Fujita M, Ohkawa Y.
  • Journal Title: PLoS Comput Biol. Volume: 17 Issue: 11 Pages: e1009579-e1009579
  • DOI: 10.1371/journal.pcbi.1009579
  • Peer Reviewed / Open Access
• [Journal Article] Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle. (2021)
  • Author(s): Christianto A, Baba T, Takahashi F, Inui K, Inoue M, Suyama M, Ono Y, Ohkawa Y, Morohashi KI.
  • Journal Title: Commun Biol. Volume: 4 Issue: 1 Pages: 1264-1264
  • DOI: 10.1038/s42003-021-02790-y
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• [Journal Article] Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development. (2021)
  • Author(s): Katada S, Takouda J, Nakagawa T, Honda M, Igarashi K, Imamura T, Ohkawa Y, Sato S, Kurumizaka H, Nakashima K.
  • Journal Title: Genes Dev. Volume: 35 Pages: 1431-1444
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• [Journal Article] Modeling population size independent tissue epigenomes by ChIL-seq with single thin sections. (2021)
  • Author(s): Maehara K, Tomimatsu K, Harada A, Tanaka K, Sato S, Fukuoka M, Okada S, Handa T, Kurumizaka H, Saitoh N, Kimura H, Ohkawa Y.
  • Journal Title: Mol Syst Biol. Volume: 17
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• [Journal Article] Genome-wide analysis of chromatin structure changes upon MyoD binding in proliferative myoblasts during the cell cycle (2021)
  • Author(s): Wu Qianmei、Fujii Takeru、Harada Akihito、Tomimatsu Kosuke、Miyawaki-Kuwakado Atsuko、Fujita Masatoshi、Maehara Kazumitsu、Ohkawa Yasuyuki
  • Journal Title: The Journal of Biochemistry Volume: - Issue: 6 Pages: 653-661
  • DOI: 10.1093/jb/mvab001
  • NAID: 40022687719
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• [Journal Article] Integrated Analysis of Transcriptome and Histone Modifications in Granulosa Cells During Ovulation in Female Mice (2021)
  • Author(s): Shirafuta Yuichiro、Tamura Isao、Ohkawa Yasuyuki、Maekawa Ryo、Doi-Tanaka Yumiko、Takagi Haruka、Mihara Yumiko、Shinagawa Masahiro、Taketani Toshiaki、Sato Shun、Tamura Hiroshi、Sugino Norihiro
  • Journal Title: Endocrinology Volume: 162 Issue: 9 Pages: 1-17
  • DOI: 10.1210/endocr/bqab128
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• [Journal Article] An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver. (2021)
  • Author(s): Matsuzaki F, Uda S, Yamauchi Y, Matsumoto M, Soga T, Maehara K, Ohkawa Y, Nakayama KI, Kuroda S, Kubota H.
  • Journal Title: Cell Rep. Volume: 36 Pages: 109569-109569
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• [Journal Article] Targeted inhibition of EPAS1-driven IL-31 production by a small-molecule compound. (2021)
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  • Journal Title: J Allergy Clin Immunol. Volume: 148 Issue: 2 Pages: 633-638
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• [Journal Article] High-depth spatial transcriptome analysis by photo-isolation chemistry. (2021)
  • Author(s): Honda M, Oki S, Kimura R, Harada A, Maehara K, Tanaka K, Meno C, Ohkawa Y.
  • Journal Title: Nat Commun. Volume: 12 Issue: 1 Pages: 4416-4416
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• [Journal Article] Transcriptome analysis of gene expression changes upon enzymatic dissociation in skeletal myoblasts. (2021)
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  • Journal Title: Genes Cells. Volume: 26 Issue: 7 Pages: 530-540
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• [Journal Article] Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle. (2021)
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  • Journal Title: Sci Adv. Volume: 7 Issue: 24
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• [Journal Article] Totipotency of mouse zygotes extends to single blastomeres of embryos at the four-cell stage. (2021)
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• [Journal Article] Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay (2021)
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• [Journal Article] Transcription factor C/EBPβ induces genome-wide H3K27ac and upregulates gene expression during decidualization of human endometrial stromal cells (2021)
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• [Journal Article] Subnuclear gene positioning through lamina association affects copper tolerance (2020)
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• [Journal Article] The role of galanin in the differentiation of mucosal mast cells in mice. (2020)
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• [Journal Article] The Dynamics of Transcriptional Activation by Hepatic Reprogramming Factors. (2020)
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• [Journal Article] Chromatin integration labeling for mapping DNA-binding proteins and modifications with low input. (2020)
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• [Journal Article] Genomic Profiling by ALaP-Seq Reveals Transcriptional Regulation by PML Bodies through DNMT3A Exclusion (2020)
  • Author(s): Kurihara Misuzu、Kato Kagayaki、Sanbo Chiaki、Shigenobu Shuji、Ohkawa Yasuyuki、Fuchigami Takeshi、Miyanari Yusuke
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  • Peer Reviewed / Open Access
• [Presentation] 単一細胞マルチオミクスによる骨格筋分化制御機構の解明 (2023)
  • Author(s): 大川恭行
  • Organizer: 第6回運動器と健康研究会
  • Invited
• [Presentation] Spatial multi-omics for understanding chromatin dynamics (2023)
  • Author(s): 大川恭行
  • Organizer: 2023年度高深度オミクスシンポジウム
  • Invited
• [Presentation] データから変化を取り出す新たな単一細胞解析技術 (2022)
  • Author(s): 大川恭行
  • Organizer: 【富士フイルム】講演
  • Invited
• [Presentation] Single-cell multi-targeted chromatin integration labeling technology for understanding chromatin dynamics (2022)
  • Author(s): Yasuyuki Ohkawa
  • Organizer: CSHA meeting on Integrative Epigenetics in Plants
  • Int'l Joint Research / Invited
• [Presentation] 空間オミクス技術によるクロマチン構造制御メカニズムの解明 (2022)
  • Author(s): 大川恭行
  • Organizer: 第95回日本生化学会大会
  • Invited
• [Presentation] 細胞恒常性を担うシグナルと遺伝子発現の制御 (2022)
  • Author(s): 大川恭行
  • Organizer: 第16回日本臨床ストレス応答学会
  • Invited
• [Presentation] 高深度解析による全ゲノムレベルの単一細胞オミクスへの挑戦 (2022)
  • Author(s): 大川恭行
  • Organizer: NGS EXPO 2022
  • Invited
• [Presentation] 単一細胞軌跡追跡によるクロマチンダイナミクスの解明 (2022)
  • Author(s): 大川恭行
  • Organizer: 2022年度国立遺伝学研究所クロマチン研究会
  • Invited
• [Presentation] Chromatin regulation during skeletal muscle regeneration (2022)
  • Author(s): Yasuyuki Ohkawa
  • Organizer: 第17回生命医科学研究所ネットワーク国際シンポジウム
  • Int'l Joint Research / Invited
• [Presentation] 骨格筋分化のクロマチンダイナミクス (2022)
  • Author(s): 大川恭行
  • Organizer: 日本遺伝学会第94回大会
  • Invited
• [Presentation] トランスクリプトミクスで迫る細胞分化能 (2022)
  • Author(s): 大川恭行
  • Organizer: 大阪大学産業科学研究所セミナー
  • Invited
• [Presentation] Spatial multi-omics for understanding gene expression regulated by cell-cell interaction. (2022)
  • Author(s): Yasuyuki Ohkawa
  • Organizer: Japan-UK Regulation through Chromatin Conference
  • Int'l Joint Research / Invited
• [Presentation] 空間オミクスによる骨格筋組織老化機序の解明 (2022)
  • Author(s): 大川恭行
  • Organizer: 第8回日本筋学会学術集会
  • Invited
• [Presentation] クロマチン解析のための新技術開発の現状と今後の展開 (2022)
  • Author(s): 大川恭行
  • Organizer: 第15回日本エピジェネティクス研究会年会
  • Invited
• [Presentation] 骨格筋再性能を制御するクロマチン構造等その破綻 (2021)
  • Author(s): 大川恭行
  • Organizer: 第94回日本生化学会大会
  • Invited
• [Presentation] 空間マルチオミクスの展開～エピゲノム, トランスクリプトームからプロテオームの空間計測の試み～ (2021)
  • Author(s): 大川恭行
  • Organizer: がん研セミナー
  • Invited
• [Presentation] Identification and Analysis of Minor Histone Variants (2021)
  • Author(s): Yasuyuki Ohkawa
  • Organizer: EMBO Workshop Physiology and function of histone variants
• [Presentation] 骨格筋特異的なヒストンが構成するクロマチン構造の解明. (2021)
  • Author(s): 大川恭行
  • Organizer: 第8回骨格筋生物学会
• [Presentation] クロマチンダイナミクスの理解に向けた同時マルチオミクスの開発. (2020)
  • Author(s): 大川恭行
  • Organizer: 『配偶子インテグリティの構築』『全能性プログラム』合同公開シンポジウム
• [Presentation] クロマチンダイナミクスの理解に向けた同時マルチオミクスの開発. (2020)
  • Author(s): 大川恭行
  • Organizer: 第43回日本分子生物学会
  • Invited
• [Presentation] トランスクリプトミクスによる骨格筋細胞分化能の解明. (2020)
  • Author(s): 大川恭行
  • Organizer: 第19回日本再生医療学会総会
  • Invited
• [Presentation] Chromatin integration labeling Technology for expanding multi-omics. (2020)
  • Author(s): 大川恭行
  • Organizer: 理研エピゲノム操作プロジェクトセミナー
  • Invited
• [Presentation] 単一細胞マルチオミクスに向けたクロマチン挿入標識法の開発. (2020)
  • Author(s): 大川恭行
  • Organizer: 第19回日本再生医療学会総会
  • Invited
• [Book] 少数細胞エピゲノム解析技術の開発 (2021)
  • Author(s): 原田 哲仁，大川 恭行
  • Publisher: 日本生化学会
• [Book] 実験医学2021年9月号 (2021)
  • Author(s): 沖 真弥、大川 恭行
  • Total Pages: 131
  • Publisher: 羊土社
  • ISBN: 9784758125475
• [Book] 遺伝子医学MOOK36 (2021)
  • Author(s): 富松航佑, 大川 恭行
  • Total Pages: 218
  • Publisher: 株式会社メディカルドゥ
• [Book] 1細胞エピゲノム解析技術開発の最前線 (2021)
  • Author(s): 大川 恭行,原田 哲仁,前原 一満
  • Total Pages: 6
  • Publisher: 医歯薬出版株式会社 週刊医学のあゆみ
• [Book] scRNA-seqを用いた細胞系譜の軌跡推定-データの背後の流れを読み取る技術-. (2020)
  • Author(s): 前原一満, 大川恭行
  • Total Pages: 8
  • Publisher: 羊土社 実験医学 増刊
• [Book] 骨格筋研究のための最先端解析技術. (2020)
  • Author(s): 原田 哲仁，大川 恭行
  • Total Pages: 7
  • Publisher: 羊土社 実験医学
• [Book] シングルセルでのエピゲノム情報の計測技術. (2020)
  • Author(s): 原田 哲仁，大川 恭行
  • Total Pages: 8
  • Publisher: 羊土社 実験医学
• [Book] 空間オミクス実現に向けたエピゲノム解析技術. (2020)
  • Author(s): 小松 哲郎，大川 恭行
  • Total Pages: 4
  • Publisher: ニューサイエンス社 月刊細胞
• [Remarks] 九州大学 トランスクリプトミクス分野ホームページ
  • URL: https://tx.bioreg.kyushu-u.ac.jp/