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Digitalization of transcription by single allele analysis

Research Project

Project/Area Number 17KT0108
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Constructive Systems Biology
Research InstitutionKyoto University

Principal Investigator

Watanabe Akira  京都大学, 医学研究科, 研究員 (60506765)

Project Period (FY) 2017-07-18 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsシングルセル / 遺伝子発現解析 / アリル特異的発現 / iPS細胞 / シングルセル遺伝子発現解析 / RNA-seq / 遺伝子 / 発現制御 / 発生・分化 / ゲノム
Outline of Final Research Achievements

We conducted single cell RNA-sequencing in combination with SNP genotyping to describe allelic regulation of the genes. Our analysis of human ES cells displayed allelic expression of genes on X chromosome, of which epigenetic status is closely linked to pluripotency of ES and iPS cells, and found several genes in prime-type ES cells were escaped from inactivation of the chromosome. In addition, we found differential regulation of allelic expression at single cell level for Amyotrophic lateral sclerosis (ALS) cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では、転写の最小の構成単位であるアリルレベルでの解析方法を提供した。従来の細胞集団を対象とした遺伝子発現解析ではできなかったX染色体のアリル転写制御を解析したことで、多能性幹細胞における分化能を判定することが可能となった。また、疾患モデル細胞における変異アリルから転写される遺伝子の解析では、疾患細胞の不均質性が示された。これらの結果は、シングルアリルレベルでの転写解析が細胞運命の理解や疾患の発症の基本原理の理解へとつながる可能性を示している。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (35 results)

All 2020 2019 2018 2017

All Journal Article (23 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells.2020

    • Author(s)
      Tsujimoto H, Kasahara T, Sueta SI, Araoka T, Sakamoto S, Okada C, Mae SI, Nakajima T, Okamoto N, Taura D, Nasu M, Shimizu T, Ryosaka M, Li Z, Sone M, Ikeya M, Watanabe A, Osafune K.
    • Journal Title

      Cell Rep.

      Volume: 31 Issue: 1 Pages: 107476-107476

    • DOI

      10.1016/j.celrep.2020.03.040

    • NAID

      120006823939

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 日常化するシングルセル遺伝子発現解析が展開する医学研究2019

    • Author(s)
      坂本智子, 渡辺 亮
    • Journal Title

      遺伝子医学

      Volume: 9 Pages: 116-121

    • NAID

      40022087132

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 医学・生物学研究に実装されるシングルセルゲノミクス2019

    • Author(s)
      渡辺 亮
    • Journal Title

      実験医学別冊「シングルセルゲノミクス」

      Volume: 37 Pages: 20-22

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 単細胞レベルでの膵内分泌細胞の不均一性と機能解明2019

    • Author(s)
      龍岡久登,坂本智子,渡辺 亮,稲垣暢也
    • Journal Title

      実験医学別冊「シングルセルゲノミクス」

      Volume: 37 Pages: 68-73

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 今村恵子,渡辺 亮,井上治久2019

    • Author(s)
      iPS細胞のシングルセル遺伝子発現解析
    • Journal Title

      実験医学別冊「シングルセルゲノミクス」

      Volume: 37 Pages: 145-148

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development.2019

    • Author(s)
      Karagiannis P, Takahashi K, Saito M, Yoshida Y, Okita K, Watanabe A, Inoue H, Yamashita JK, Todani M, Nakagawa M, Osawa M, Yashiro Y, Yamanaka S, Osafune K.
    • Journal Title

      Physiol Rev

      Volume: 99 Issue: 1 Pages: 78-114

    • DOI

      10.1152/physrev.00039.2017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] シングルセルゲノミクスによる細胞個性の解析が展開する免疫学研究.2019

    • Author(s)
      坂本智子、渡辺亮
    • Journal Title

      臨床免疫・アレルギー科,

      Volume: 71 Pages: 448-454

    • NAID

      40021866266

    • Related Report
      2018 Research-status Report
  • [Journal Article] Enhancing T cell Receptor Stability in Rejuvenated iPSC-derived T cells improves their use in cancer immunotherapy2018

    • Author(s)
      Minagawa A, Yoshikawa T, Yasukawa M, Hotta A, Kunitomo M, Iriguchi S, Takiguchi M, Kassai Y, Imai E, Yasui Y, Kawai Y, Zhang R, Uemura Y, Miyoshi H, Nakanishi M, Watanabe A, Hayashi A, Kawana K, Fujii T, Nakatsura T, Kaneko S
    • Journal Title

      Cell Stem Cell

      Volume: 23 Issue: 6 Pages: 850-858

    • DOI

      10.1016/j.stem.2018.10.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integration Capacity of Human Induced Pluripotent Stem Cell-Derived Cartilage.2018

    • Author(s)
      Chen X, Yamashita A, Morioka M, Senba T, Kamatani T, Watanabe A, Kosai A, Tsumaki N.
    • Journal Title

      Tissue Eng Part A,

      Volume: 25 Issue: 5-6 Pages: 437-445

    • DOI

      10.1089/ten.tea.2018.0133

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA.2018

    • Author(s)
      Higaki K, Hirao M, Kawana-Tachikawa A, Iriguchi S, Kumagai A, Ueda N, Bo W, Kamibayashi S, Watanabe A, Nakauchi H, Suzuki K, Kaneko S.
    • Journal Title

      Mol Ther Nucleic Acids

      Volume: 12 Pages: 723-804

    • DOI

      10.1016/j.omtn.2018.07.017

    • NAID

      120006649570

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.2018

    • Author(s)
      Ueda N, Uemura Y, Zhang R, Kitayama S, Iriguchi S, Kawai Y, Yasui Y, Tatsumi M, Ueda T, Liu TY, Mizoro Y, Okada C, Watanabe A, Nakanishi M, Senju S, Nishimura Y, Kuzushima K, Kiyoi H, Naoe T, Kaneko S
    • Journal Title

      Stem Cell Reports

      Volume: 10 Issue: 6 Pages: 1935-1946

    • DOI

      10.1016/j.stemcr.2018.04.025

    • NAID

      120006473765

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MYC Releases Early Reprogrammed Human Cells from Proliferation Pause via Retinoblastoma Protein Inhibition.2018

    • Author(s)
      Rand TA, Sutou K, Tanabe K, Jeong D, Nomura M, Kitaoka F, Tomoda E, Narita M, Nakamura M, Nakamura M, Watanabe A, Rulifson E, Yamanaka S, Takahashi K.
    • Journal Title

      Cell Rep.

      Volume: 23 Issue: 2 Pages: 361-375

    • DOI

      10.1016/j.celrep.2018.03.057

    • NAID

      120006463741

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 細胞運命決定機構を明らかにするシングルセル遺伝子発現解析.2018

    • Author(s)
      坂本智子、前伸一、長船健二、岡田千尋、樺井良太朗、渡辺亮.
    • Journal Title

      日本薬理学雑誌

      Volume: 153 Pages: 61-66

    • NAID

      130007595895

    • Related Report
      2018 Research-status Report
  • [Journal Article] Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors2018

    • Author(s)
      Oshima Koichi、Watanabe Akira、Nakahata Tatsutoshi、Saito Megumu K. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 497 Issue: 2 Pages: 719-725

    • DOI

      10.1016/j.bbrc.2018.02.139

    • NAID

      120006466601

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] シングルセル解析の最前線2018

    • Author(s)
      渡辺亮、坂本智子
    • Journal Title

      整形・災害外科

      Volume: 61 Pages: 427-431

    • Related Report
      2017 Research-status Report
  • [Journal Article] Adrenergic receptor agonists induce the differentiation of pluripotent stem cell-derived hepatoblasts into hepatocyte-like cells2017

    • Author(s)
      Kotaka Maki、Toyoda Taro、Yasuda Katsutaro、Kitano Yuko、Okada Chihiro、Ohta Akira、Watanabe Akira、Uesugi Motonari、Osafune Kenji
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 16734-16734

    • DOI

      10.1038/s41598-017-16858-5

    • NAID

      120006817602

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin-producing cells derived from ‘induced pluripotent stem cells’ of patients with fulminant type 1 diabetes: Vulnerability to cytokine insults and increased expression of apoptosis-related genes2017

    • Author(s)
      Hosokawa Yoshiya、Toyoda Taro、Fukui Kenji、Baden Megu Yamaguchi、Funato Michinori、Kondo Yasushi、Sudo Tomomi、Iwahashi Hiromi、Kishida Marina、Okada Chihiro、Watanabe Akira、Asaka Isao、Osafune Kenji、Imagawa Akihisa、Shimomura Iichiro
    • Journal Title

      Journal of Diabetes Investigation

      Volume: - Issue: 3 Pages: 481-493

    • DOI

      10.1111/jdi.12727

    • NAID

      120006498249

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rho-Associated Kinases and Non-muscle Myosin IIs Inhibit the Differentiation of Human iPSCs to Pancreatic Endoderm2017

    • Author(s)
      Toyoda Taro、Kimura Azuma、Tanaka Hiromi、Ameku Tomonaga、Mima Atsushi、Hirose Yurie、Nakamura Masahiro、Watanabe Akira、Osafune Kenji
    • Journal Title

      Stem Cell Reports

      Volume: 9 Issue: 2 Pages: 419-428

    • DOI

      10.1016/j.stemcr.2017.07.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] iPSC-based drug repositioning identifies Src/c-Abl as a therapeutic target for ALS motor neurons2017

    • Author(s)
      Imamura K, Izumi Y, 他24名, Hosokawa M, Akiyama H, Ayaki T, Ito H, Takahashi R, Yamanaka S, Inoue H
    • Journal Title

      Science Translational Medicine

      Volume: 9 Issue: 391 Pages: 391-391

    • DOI

      10.1126/scitranslmed.aaf3962

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of a small molecule that facilitates the differentiation of human iPSCs/ESCs and mouse embryonic pancreatic explants into pancreatic endocrine cells2017

    • Author(s)
      Kondo Yasushi、Toyoda Taro、Ito Ryo、Funato Michinori、Hosokawa Yoshiya、Matsui Satoshi、Sudo Tomomi、Nakamura Masahiro、Okada Chihiro、Zhuang Xiaotong、Watanabe Akira、Ohta Akira、Inagaki Nobuya、Osafune Kenji
    • Journal Title

      Diabetologia

      Volume: 60 Issue: 8 Pages: 1454-1466

    • DOI

      10.1007/s00125-017-4302-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxic adaptation of leukemic cells infiltrating the CNS affords a therapeutic strategy targeting VEGFA2017

    • Author(s)
      Kato Itaru、Nishinaka Yoko、Nakamura Masahiro、et al.
    • Journal Title

      Blood

      Volume: 129 Issue: 23 Pages: 3126-3129

    • DOI

      10.1182/blood-2016-06-721712

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 幹細胞・発生研究とシングルセル解析2017

    • Author(s)
      渡辺亮
    • Journal Title

      実験医学別冊「シングルセル解析プロトコール」.

      Volume: - Pages: 26-32

    • Related Report
      2017 Research-status Report
  • [Journal Article] エピゲノムデータベースの現状と活用2017

    • Author(s)
      渡辺亮、中村正裕、岡田千尋
    • Journal Title

      実験医学別冊「エピジェネティクス実験スタンダード」

      Volume: - Pages: 1917-211

    • Related Report
      2017 Research-status Report
  • [Presentation] システムズシングルセルオミックスで迫る細胞運命と医療への展開2019

    • Author(s)
      渡辺 亮
    • Organizer
      第83回 生化学会中部支部 例会・シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] シングルセルゲノミクスで実践する医学研究2019

    • Author(s)
      渡辺 亮
    • Organizer
      第78回 日本癌学会 学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] エピジェネティクスが解き明かすがんと発生2019

    • Author(s)
      第13回エピジェネティクス研究会年会
    • Organizer
      第13回エピジェネティクス研究会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Epigenetic Landscape in Multi-step Leukemogenesis in Down Syndrome.2018

    • Author(s)
      Akira Watanabe
    • Organizer
      International Symposium on Epigenome 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] シングルセル遺伝子発現解析が変える生命科学.2018

    • Author(s)
      渡辺亮
    • Organizer
      第41回 分子生物学会 年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Epigenetic Dysregulation is a Key Signature in Multi-step Leukemogenesis in Down Syndrome.2018

    • Author(s)
      Akira Watanabe
    • Organizer
      第80回 日本血液学会 学術総会.
    • Related Report
      2018 Research-status Report
  • [Presentation] 腫瘍学及び再生医療に応用されるシングルセルマルチオミックス2018

    • Author(s)
      渡辺亮
    • Organizer
      第77回 日本癌学会 学術総会.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] シングルセル遺伝子発現解析で迫る細胞運命決定機構2018

    • Author(s)
      渡辺亮
    • Organizer
      生命医薬情報学連合大会2018.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 膵臓の再生を明らかにするシングルセル遺伝子発現及びマルチオミックス解析.2018

    • Author(s)
      渡辺亮
    • Organizer
      第61回日本糖尿病学会 年次学術集会.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Challenge to Regeneration of Hair Cells in the Cochlea Sensory Epithelia by Single Cell Transcriptomics.2018

    • Author(s)
      喜多 知子、坂本 智子、松永 麻美、長谷川 晶子、岡田 千尋、中川 隆之、渡辺 亮.
    • Organizer
      Challenge to Regeneration of Hair Cells in the Cochlea Sensory Epithelia by Single Cell Transcriptomics.第41回 分子生物学会 年会.
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵臓の再生を明らかにするシングルセル遺伝子発現解析.2018

    • Author(s)
      坂本 智子、龍岡 久登、矢部 大介、稲垣 暢也、渡辺 亮.
    • Organizer
      第41回 分子生物学会 年会
    • Related Report
      2018 Research-status Report
  • [Book] 実験医学増刊「シングルセルゲノミクス」2019

    • Author(s)
      渡辺 亮、鈴木 穣(編)
    • Total Pages
      219
    • Publisher
      羊土社
    • ISBN
      9784758103831
    • Related Report
      2019 Annual Research Report

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Published: 2017-07-21   Modified: 2021-02-19  

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