Single cell proteomics to molecular characterization of cancer stem cells

• Project/Area Number: 16H04730
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: System genome science
• Research Institution: Kyushu University
• Principal Investigator: Masaki Matsumoto 九州大学, 生体防御医学研究所, 准教授 (60380531)
• Research Collaborator: Nakayama Keiichi ; Bamba Takeshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000); Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: プロテオミクス / １細胞分析 / がん幹細胞 / シングルセル / プロテオーム / シングルセル解析 / バイオテクノロジー

Outline of Final Research Achievements

We have developed a new targeted proteomics platform―in vitro proteome assisted MRM for protein absolute quantification (iMPAQT)― using >18,000 human recombinant proteins for genome-wide protein absolute quantification (Matsumoto et al., Nature Methods, 2017). Improvements of sample preparation and sample loading system enable us to measure proteome in very small amount of sample. We found that a cell cycle regulator, p57 protein is a good marker for cancer stem cell. On the basis of the expression of p57, cancer stem cells were effectively enriched. Finally, we performed multi-omics approach to identify the molecular signature of cancer stem cells.

Academic Significance and Societal Importance of the Research Achievements

本研究によって次世代型の定量プロテオミクスの技術基盤を確立することができた。これは、汎用的に利用されている手法と比べて精度や特異性において優れており、生命科学におけるタンパク質の解析に革新をもたらすことが期待される。さらに、高感度化によって小数細胞プロテオーム解析を実現可能としたことで、がん幹細胞の特徴を分子レベルで捉えることができるようなったことは、がんの根治を目指す医学研究を大いに促すものである。

Research Products

• [Journal Article] Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16 (2018)
  • Author(s): Hosokawa Hiroyuki、Romero-Wolf Maile、Yui Mary A.、Ungerb?ck Jonas、Quiloan Maria L. G.、Matsumoto Masaki、Nakayama Keiichi I.、Tanaka Tomoaki、Rothenberg Ellen V.
  • Journal Title: Nature Immunology Volume: 19 Issue: 12 Pages: 1427-1440
  • DOI: 10.1038/s41590-018-0238-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of the physiological substrates of PDIp, a pancreas-specific protein-disulfide isomerase family member (2018)
  • Author(s): Fujimoto Takushi、Nakamura Orie、Saito Michiko、Tsuru Akio、Matsumoto Masaki、Kohno Kenji、Inaba Kenji、Kadokura Hiroshi
  • Journal Title: Journal of Biological Chemistry Volume: 293 Issue: 48 Pages: 18421-18433
  • DOI: 10.1074/jbc.ra118.003694
  • Peer Reviewed / Open Access
• [Journal Article] Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding (2018)
  • Author(s): Hosokawa Hiroyuki、Ungerb?ck Jonas、Wang Xun、Matsumoto Masaki、Nakayama Keiichi I.、Cohen Sarah M.、Tanaka Tomoaki、Rothenberg Ellen V.
  • Journal Title: Immunity Volume: 48 Issue: 6 Pages: 1119-1134.e7
  • DOI: 10.1016/j.immuni.2018.04.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks (2018)
  • Author(s): Kawata Kentaro、Hatano Atsushi、Yugi Katsuyuki、Kubota Hiroyuki、Sano Takanori、Fujii Masashi、Tomizawa Yoko、Kokaji Toshiya、Tanaka Kaori Y.、Uda Shinsuke、Suzuki Yutaka、Matsumoto Masaki、Nakayama Keiichi I.、Saitoh Kaori、Kato Keiko、Ueno Ayano、Ohishi Maki、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
  • Journal Title: iScience Volume: 7 Pages: 212-229
  • DOI: 10.1016/j.isci.2018.07.022
  • Peer Reviewed / Open Access
• [Journal Article] The jPOST environment: an integrated proteomics data repository and database (2018)
  • Author(s): Moriya Yuki、Kawano Shin、Okuda Shujiro、Watanabe Yu、Matsumoto Masaki、Takami Tomoyo、Kobayashi Daiki、Yamanouchi Yoshinori、Araki Norie、Yoshizawa Akiyasu C、Tabata Tsuyoshi、Iwasaki Mio、Sugiyama Naoyuki、Tanaka Satoshi、Goto Susumu、Ishihama Yasushi
  • Journal Title: Nucleic Acids Research Volume: 47 Issue: D1 Pages: 1218-1224
  • DOI: 10.1093/nar/gky899
  • Peer Reviewed / Open Access
• [Journal Article] The promise of targeted proteomics for quantitative network biology (2018)
  • Author(s): Matsumoto Masaki、Nakayama Keiichi I
  • Journal Title: Current Opinion in Biotechnology Volume: 54 Pages: 88-97
  • DOI: 10.1016/j.copbio.2018.02.014
  • Peer Reviewed
• [Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth. (2018)
  • Author(s): M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
  • Journal Title: Cancer Cell Volume: 12 Issue: 3 Pages: 355-367
  • DOI: 10.1016/j.ccell.2018.02.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages (2017)
  • Author(s): Nakatsumi Hirokazu、Matsumoto Masaki、Nakayama Keiichi I.
  • Journal Title: Cell Reports Volume: 21 Issue: 9 Pages: 2471-2486
  • DOI: 10.1016/j.celrep.2017.11.014
  • Peer Reviewed / Open Access
• [Journal Article] Robotic crowd biology with Maholo LabDroids. (2017)
  • Author(s): Yachie N; Robotic Biology Consortium (inc. Masaki Matsumoto)., Natsume T.
  • Journal Title: Nature Biotechnology Volume: 35 Issue: 4 Pages: 310-312
  • DOI: 10.1038/nbt.3758
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Small Nucleolar Noncoding RNA SNORA23, Upregulated in Human Pancreatic Ductal Adenocarcinoma, Regulates Expression of SYNE2 to Promote Growth and Metastasis of Xenograft Tumors in Mice. (2017)
  • Author(s): Cui L, Nakano K, Obchoei S, Setoguchi K, Matsumoto M, Yamamoto T, Obika S, Shimada K, Hiraoka N.
  • Journal Title: Gastroenterology Volume: 印刷中 Issue: 1 Pages: 292-306.e2
  • DOI: 10.1053/j.gastro.2017.03.050
  • Peer Reviewed
• [Journal Article] A large-scale targeted proteomics assay resource based on an in vitro human proteome. (2017)
  • Author(s): Matsumoto M, Matsuzaki F, Oshikawa K, Goshima N, Mori M, Kawamura Y, Ogawa K, Fukuda E, Nakatsumi H, Natsume T, Fukui K, Horimoto K, Nagashima T, Funayama R, Nakayama K, Nakayama KI.
  • Journal Title: Nat Methods Volume: 14 Issue: 3 Pages: 251-258
  • DOI: 10.1038/nmeth.4116
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of KIAA1210 as a novel X-chromosome-linked protein that localizes to the acrosome and associates with the ectoplasmic specialization in testes. (2017)
  • Author(s): Iwamori T, Iwamori N, Matsumoto M, Ono E, Matzuk MM.
  • Journal Title: Biol Reprod Volume: 96 Issue: 2 Pages: 469-477
  • DOI: 10.1095/biolreprod.116.145458
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. (2017)
  • Author(s): Matsumoto A, Pasut A, Matsumoto M, Yamashita R, Fung J, Monteleone E, Saghatelian A, Nakayama KI, Clohessy JG, Pandolfi PP.
  • Journal Title: Nature Volume: 541 Issue: 7636 Pages: 228-232
  • DOI: 10.1038/nature21034
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] jPOSTrepo: an international standard data repository for proteomes. (2017)
  • Author(s): Okuda S, Watanabe Y, Moriya Y, Kawano S, Yamamoto T, Matsumoto M, Takami T, Kobayashi D, Araki N, Yoshizawa AC, Tabata T, Sugiyama N, Goto S, Ishihama Y.
  • Journal Title: Nucleic Acids Res. Volume: 45 Issue: D1 Pages: D1107-D1111
  • DOI: 10.1093/nar/gkw1080
  • NAID: 120006353864
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GRWD1 negatively regulates p53 via the RPL11-MDM2 pathway and promotes tumorigenesis. (2017)
  • Author(s): Kayama K, Watanabe S, Takafuji T, Tsuji T, Hironaka K, Matsumoto M, Nakayama KI, Enari M, Kohno T, Shiraishi K, Kiyono T, Yoshida K, Sugimoto N, Fujita M.
  • Journal Title: EMBO Rep. Volume: 18 Issue: 1 Pages: 123-137
  • DOI: 10.15252/embr.201642444
  • Peer Reviewed
• [Journal Article] The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes. (2016)
  • Author(s): Mizushima, W., Takahashi , H., Watanabe, M., Kinugawa, S., Matsushima, S., Takada, S., Yokota, T., Furihata, T., Matsumoto, J., Tsuda, M., Chiba, I., Nagashima, S., Yanagi, S., Matsumoto, M., Nakayama, K.I., Tsutsui, H. and Hatakeyama, S.
  • Journal Title: J. Mol. Cell. Cardiol. Volume: 100 Pages: 43-53
  • DOI: 10.1016/j.yjmcc.2016.09.013
  • NAID: 120006360069
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phosphoproteomics analyses show subnetwork systems in T-cell receptor signaling. (2016)
  • Author(s): Hatano A, Matsumoto M, Nakayama KI.
  • Journal Title: Genes Cells. Volume: 21 Issue: 10 Pages: 1095-1112
  • DOI: 10.1111/gtc.12406
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of the Arabidopsis bHLH transcription factor by monomerization through abscisic acid-induced phosphorylation. (2016)
  • Author(s): Takahashi Y, Kinoshita T, Matsumoto M, Shimazaki K.
  • Journal Title: Plant Journal Volume: 87 Issue: 6 Pages: 559-567
  • DOI: 10.1111/tpj.13217
  • Peer Reviewed / Open Access
• [Journal Article] Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes (2016)
  • Author(s): Fujieda Y., Amengual O., Matsumoto M., Kuroki K., Takahashi H., Kono M., Kurita Y., Otomo K., Kato M., Oku K., Bohgaki T., Horita T., Yasuda S., Maenaka K., Hatakeyama S., Nakayama K.I. and Atsumi T. et al.
  • Journal Title: Rheumatology Volume: 印刷中 Issue: 6 Pages: 1117-1126
  • DOI: 10.1093/rheumatology/kew005
  • Peer Reviewed / Open Access
• [Presentation] Robotics promotes accurate and reproducible data acquisition in proteomics (2018)
  • Author(s): Masaki Matsumoto
  • Organizer: Robotics and Semantic Systems for Biology Symposium 2
  • Int'l Joint Research / Invited
• [Presentation] iMPAQT: A platform for large scale targeted proteomics based on in vitro human proteome. (2017)
  • Author(s): Masaki Matsumoto
  • Organizer: 1st-Internatinal Symposium of the Kyoto Biomolecular Mass Spectrometry Society.
  • Place of Presentation: 京都大学
  • Year and Date: 2017-02-07
  • Int'l Joint Research / Invited
• [Presentation] iMPAQT: A Platform for Large-Scale Targeted Proteomics Based on an in Vitro Human Proteome (2017)
  • Author(s): ②松本雅記、中山敬一
  • Organizer: JPrOS2017年大会
• [Presentation] iMPAQT: A platform for large-scale targeted proteomics based on an in vitro human proteome (2017)
  • Author(s): ③松本雅記
  • Organizer: 第65質量分析総合討論会
  • Invited
• [Presentation] iMPAQT: 組換えタンパク質を利用したタンパク質絶対定量プラットフォーム～がん代謝研究への応用～ (2016)
  • Author(s): 松本雅記
  • Organizer: 第4回次世代がんインフォマティクス研究会
  • Place of Presentation: 岡山大学工学部
  • Year and Date: 2016-12-16
  • Invited
• [Presentation] 定量プロテオミクスプラットフォームのためのインフォマティクス (2016)
  • Author(s): 松本雅記
  • Organizer: 質量分析インフォマティクス研究会・第1回ワークショップ
  • Place of Presentation: JST東京本部（サイエンスプラザ）
  • Year and Date: 2016-10-07
  • Invited
• [Remarks] iMPAQT knowledge DB
  • URL: http://impaqt.jpost.org/iMPAQT/