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Dissecting Cell Fate Decision by Single Cell Genomics

Research Project

Project/Area Number 15K06921
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field System genome science
Research InstitutionKyoto University

Principal Investigator

Watanabe Akira  京都大学, iPS細胞研究所, 特定拠点助教 (60506765)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsシングルセル / 遺伝子発現 / iPS細胞 / RNA-seq / ATAC-seq / 心筋細胞 / シングルセル解析
Outline of Final Research Achievements

Human pluripotent stem cell-derived cardiomyocytes show promise for clinical application. To reach this potential, however, improved maturity and reduced cellular heterogeneity of in vitro differentiated cardiomyocytes is needed. Here, we addressed transcriptional heterogeneity in induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) by single-cell RNA sequencing. We successfully defined differentiation states at the single-cell level and clarified heterogeneities in the gene expression patterns of iPSC-CMs, especially those cultured over long periods. We developed a novel maturation index to perform in silico sorting and score the maturation level of the cells. Additionally, we identified a new cell surface marker of mature iPSC-CMs by which we could enrich well-matured iPSC-CMs from a heterogeneous population of iPSC-CMs. Our single-cell RNA sequencing approach could help clarify variation of in vitro differentiated cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016 2015

All Journal Article (21 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 18 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results)

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

    • Author(s)
      10.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 Annual Research Report
  • [Journal Article] Autologous Induced Stem Cell-Derived Retinal Cells for Macular Degeneration2017

    • Author(s)
      M. Mandai, A. Watanabe, Y. Kurimoto, 他36名
    • Journal Title

      New England Journal of Medicine

      Volume: 376 Issue: 11 Pages: 1038-1046

    • DOI

      10.1056/nejmoa1608368

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of a High-Frequency Somatic NLRC4 Mutation as a Cause of Autoinflammation by Pluripotent Cell-Based Phenotype Dissection.2017

    • Author(s)
      Kawasaki Y, Oda H, Ito J, Niwa A, Tanaka T, Hijikata A, Seki R, Nagahashi A, Osawa M, Asaka I, Watanabe A, Nishimata S, Shirai T, Kawashima H, Ohara O, Nakahata T, Nishikomori R, Heike T, Saito MK.
    • Journal Title

      Arthritis Rheumatol.

      Volume: 69 Issue: 2 Pages: 447-459

    • DOI

      10.1002/art.39960

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.2017

    • Author(s)
      Sugiyama H, Takahashi K, Yamamoto T, Iwasaki M, Narita M, Nakamura M, Rand TA, Nakagawa M, Watanabe A, Yamanaka S.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114 Issue: 2 Pages: 340-345

    • DOI

      10.1073/pnas.1617234114

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transcriptional Analysis of Intravenous Immunoglobulin Resistance in Kawasaki Disease Using an Induced Pluripotent Stem Cell Disease Model2017

    • Author(s)
      Ikeda K, Mizoro Y, Ameku T, Nomiya Y, Mae SI, Matsui S, Kuchitsu Y, Suzuki C, Hamaoka-Okamoto A, Yahata T, Sone M, Okita K, Watanabe A, Osafune K, Hamaoka K.
    • Journal Title

      Circulation Journal

      Volume: 81 Issue: 1 Pages: 110-118

    • DOI

      10.1253/circj.CJ-16-0541

    • NAID

      130005252647

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Redefining definitive endoderm subtypes by robust induction of human induced pluripotent stem cells.2016

    • Author(s)
      Matsuno K, Mae SI, Okada C, Nakamura M, Watanabe A, Toyoda T, Uchida E, Osafune K.
    • Journal Title

      Differentiation

      Volume: 92 Issue: 5 Pages: 281-290

    • DOI

      10.1016/j.diff.2016.04.002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells.2016

    • Author(s)
      Ohta R., Niwa A., Taniguchi Y., Suzuki NM., Toga J., Yagi E., Saiki N., Nishinaka-Arai Y., Okada C., Watanabe A., Nakahata T., Sekiguchi K., Saito MK.
    • Journal Title

      Scientific Reports

      Volume: - Issue: 1 Pages: 35680-35680

    • DOI

      10.1038/srep35680

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1.2016

    • Author(s)
      Samata B, Doi D, Nishimura K, Kikuchi T, Watanabe A, Sakamoto Y, Kakuta J, Ono Y, Takahashi J.
    • Journal Title

      Nat Commun.

      Volume: 4 Issue: 1 Pages: 13907-13907

    • DOI

      10.1038/ncomms13097

    • NAID

      120005867037

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic Variation between Human Induced Pluripotent Stem Cell Lines Is an Indicator of Differentiation Capacity2016

    • Author(s)
      ③M. Nishizawa, K. Chonabayashi, M. Nomura, A. Tanaka, M. Nakamura, A. Inagaki, M. Nishikawa, I. Takei, A. Oishi, K. Tanabe, M. Ohnuki, H. Yokota, M. Koyanagi-Aoi, K. Okita, A. Watanabe, A. Takaori-Kondo, S. Yamanaka, Y. Yoshida
    • Journal Title

      Cell Stem Cell

      Volume: 19 Issue: 3 Pages: 341-354

    • DOI

      10.1016/j.stem.2016.06.019

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.2016

    • Author(s)
      Ameku T, Watanabe A, Osafune K et al.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 30013-30013

    • DOI

      10.1038/srep30013

    • NAID

      120005825896

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modeling the early phenotype at the euromuscular junction of spinal muscular atrophy using patient-derived iPSCs.2015

    • Author(s)
      Yoshida, M., Kitaoka, S., Egawa N., Yamane M., Ikeda R., Tsukita K., Amano N., Watanabe A., Morimoto, M., Takahashi J., Hosoi H., Nakahatan, T., Inoue, H.,Saito, Megumu K.
    • Journal Title

      Stem Cell Reports

      Volume: 4 Issue: 4 Pages: 1-8

    • DOI

      10.1016/j.stemcr.2015.02.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pluripotent cell models of Fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.2015

    • Author(s)
      Suzuki NM, Niwa A, Yabe M, Hira A, Okada C, Amano N, Watanabe A, Watanabe K, Heike T, Takata M, Nakahata T, Saito MK
    • Journal Title

      Stem Cells Transl Med

      Volume: 4 Issue: 4 Pages: 333-338

    • DOI

      10.5966/sctm.2013-0172

    • NAID

      120005980869

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] シングルセル解析によって可視化する臓器の発生過程2016

    • Author(s)
      渡辺 亮
    • Organizer
      第64回日本輸血・細胞治療学会
    • Place of Presentation
      京都
    • Year and Date
      2016-04-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 臓器の発生過程を可視化するシングルセル遺伝子発現解析2015

    • Author(s)
      渡辺 亮
    • Organizer
      第38回分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] シングルセル遺伝子解析が明らかにするヒト発生過程における細胞運命の決定2015

    • Author(s)
      渡辺 亮
    • Organizer
      第67回日本生物工学会大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2015-10-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] The Single Cell Epigenetics Dissects Cell Fate Specification2015

    • Author(s)
      Akira Watanabe
    • Organizer
      Top Global University Japan, 1st Joint Symposium of International Partners
    • Place of Presentation
      京都
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Single Cell Transcriptome Analysis Dissects Cell Fate Specification2015

    • Author(s)
      Akira Watanabe
    • Organizer
      第53回生物物理学会年会
    • Place of Presentation
      金沢
    • Year and Date
      2015-09-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 臓器の発生過程を可視化するシングルセル遺伝子解析2015

    • Author(s)
      渡辺 亮
    • Organizer
      第26回臨床口腔病理学会総会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2015-07-29
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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