Distribution analysis of S1P on tissue sections by high resolution MS imaging

• Project/Area Number: 20H03374
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Teikyo University (2021-2022); Tohoku University (2020)
• Principal Investigator: Saigusa Daisuke 帝京大学, 薬学部, 准教授 (90545237)
• Co-Investigator(Kenkyū-buntansha): 可野 邦行 東京大学, 大学院薬学系研究科(薬学部), 助教 (50636404) ; 松本 洋太郎 東北大学, 薬学研究科, 講師 (90420041)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2022: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2020: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: S1P / MALDI / MSイメージング / 質量分析計 / スフィンゴ脂質 / MSイメージング法 / 一細胞 / 誘導体化

Outline of Research at the Start

スフィンゴシン一リン酸（S1P）は、生理活性脂質の一種であり、生体内における免疫機能の制御への関連が明らかにされている。また、がんを含む病気の発症にも関わることから、S1Pシグナル伝達系に含まれる分子機構の解明による創薬標的分子の同定が期待されている。しかしながら、これまでに生体組織を用いたS1Pの機能解析において、細胞分布を組織切片上で直接可視化することはできなかった。
本研究は、我々が開発した質量分析イメージング法によるS1P可視化法を一細胞レベルの解析技術に発展させ、S1Pの分子機能解析に応用することで新たな創薬標的の同定し、未来型医療に貢献する成果を創出することを目的としている。

Outline of Final Research Achievements

Sphingosine monophosphate (S1P)　is a bioactive lipid and has been implicated in the pathogenesis of immunological diseases, cancer, and atherosclerosis. S1P and its related molecules expressed in their signaling pathway are considered potential drug targets. However, it has been difficult to visualize the tissue distribution of S1P using conventional analytical methods. In this study, we developed a S1P-specific detection method and a highly sensitive and high-resolution tissue section by MS imaging. We constructed a library of Phostag derivatization reagents by synthesizing novel Phostag derivatization reagents, and succeeded in highly sensitive detection of S1P.

Academic Significance and Societal Importance of the Research Achievements

我々は、S1Pを高感度に検出できる新規Phostag試薬の合成に成功した。本研究では、Phostag誘導体化試薬を複数種合成したことにより、Phostagライブラリーを構築したが、この試薬類は様々な化合物に対して応用できる可能性が考えられるため、学術的な意義が高い。また、S1P関連疾患に対する分子メカニズム解析にも有用であり、疾患解明に貢献するため社会的意義が高いと考えられる。本研究により新たな創薬に役立つことが期待される。

Research Products

• [Journal Article] Decreased β‐hydroxybutyrate and ketogenic amino acid levels in depressed human adults (2023)
  • Author(s): Sato Shiho、Yu Zhiqian、Sakai Mai、Motoike Ikuko N.、Saigusa Daisuke、Hirayama Ryo、Kikuchi Yoshie、Abe Takaaki、Kinoshita Kengo、Koshiba Seizo、Tomita Hiroaki
  • Journal Title: European Journal of Neuroscience Volume: 57 Issue: 6 Pages: 1018-1032
  • DOI: 10.1111/ejn.15931
  • Peer Reviewed / Open Access
• [Journal Article] Multiomics and artificial intelligence enabled peripheral blood-based prediction of amnestic mild cognitive impairment. (2023)
  • Author(s): Tatara Y, Yamazaki H, Katsuoka F, Chiba M, Saigusa D, Kasai S, Nakamura T, Inoue J, Aoki Y, Shoji M, Motoike I, Tamada Y, Hashizume K, Shoji M, Kinoshita K, Murashita K, Nakaji S, Yamamoto M, Itoh K.
  • Journal Title: Current Research in Translational Medicine. Volume: 71 Issue: 1 Pages: 103367-103367
  • DOI: 10.1016/j.retram.2022.103367
  • Peer Reviewed / Open Access
• [Journal Article] Lipidomic and metabolic profiling of plasma and plasma-derived extracellular vesicles by UHPLC-MS/MS (2022)
  • Author(s): Daisuke Saigusa、Takeshi Honda、Yuko Iwasaki、Koji Ueda、Eiji Hishinuma、Naomi Matsukawa、Akira Togashi、Noriyuki Matsutani、Nobuhiko Seki
  • Journal Title: Medical Mass Spectrometry Volume: 6 Issue: 2 Pages: 126-137
  • DOI: 10.24508/mms.2022.11.007
  • ISSN: 2432-7441, 2432-745X
  • Year and Date: 2022-11-25
  • Peer Reviewed / Open Access
• [Journal Article] Quantification of threonine-containing lysophospholipids using ESI-LC-MS/MS in mouse tissues (2022)
  • Author(s): Michiyo Okudaira、Kuniyuki Kano、Kumiko Makide、Daisuke Saigusa、Tomohiko Ohwada、Junken Aoki
  • Journal Title: Medical Mass Spectrometry Volume: 6 Issue: 2 Pages: 138-148
  • DOI: 10.24508/mms.2022.11.008
  • ISSN: 2432-7441, 2432-745X
  • Year and Date: 2022-11-25
  • Peer Reviewed / Open Access
• [Journal Article] Modulations of bioactive lipids and their receptors in postmortem Alzheimer's disease brains. (2022)
  • Author(s): Kurano M, Saito Y, Uranbileg B, Saigusa D, Kano K, Aoki J, Yatomi Y.
  • Journal Title: Front Aging Neurosci Volume: 14 Pages: 1066578-1066578
  • DOI: 10.3389/fnagi.2022.1066578
  • Peer Reviewed / Open Access
• [Journal Article] Plasma metabolic disturbances during pregnancy and postpartum in women with depression (2022)
  • Author(s): Z Yu, N Matsukawa, D Saigusa, I. N. Motoike, C Ono, Y Okamura, T Onuma, Y Takahashi, M Sakai, H Kudo, T Obara, K Murakami, M Shirota, S Kikuchi, N Kobayashi, Y Kikuchi, J Sugawara, N Minegishi, S Ogishima, K Kinoshita, M Yamamoto, N Yaegashi, S Kuriyama, S Koshiba, H Tomita
  • Journal Title: iScience Volume: 25(12) Issue: 12 Pages: 105666-105666
  • DOI: 10.1016/j.isci.2022.105666
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dynamic modulations of urinary sphingolipid and glycerophospholipid levels in COVID-19 and correlations with COVID-19-associated kidney injuries (2022)
  • Author(s): Kurano Makoto、Jubishi Daisuke、Okamoto Koh、Hashimoto Hideki、Sakai Eri、Morita Yoshifumi、Saigusa Daisuke、Kano Kuniyuki、Aoki Junken、Harada Sohei、Okugawa Shu、Doi Kent、Moriya Kyoji、Yatomi Yutaka
  • Journal Title: Journal of Biomedical Science Volume: 29 Issue: 1 Pages: 1069-1087
  • DOI: 10.1186/s12929-022-00880-5
  • Peer Reviewed / Open Access
• [Journal Article] Codon Usage and mRNA Stability are Translational Determinants of Cellular Response to Canonical Ferroptosis Inducers (2022)
  • Author(s): Rashad Sherif、Byrne Shane R、Saigusa Daisuke、Xiang Jingdong、Zhou Yuan、Zhang Liyin、Begley Thomas J、Tominaga Teiji、Niizuma Kuniyasu
  • Journal Title: Neuroscience Volume: 501 Pages: 103-130
  • DOI: 10.1016/j.neuroscience.2022.08.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Introducing the Lipidomics Minimal Reporting Checklist (2022)
  • Author(s): McDonald Jeffrey G.、Ejsing Christer S.、Kopczynski Dominik、他29名
  • Journal Title: Nature Metabolism Volume: 4 Issue: 9 Pages: 1086-1088
  • DOI: 10.1038/s42255-022-00628-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolic and Epigenetic Regulation of SMAD7 by STC1 Ameliorates Lung Fibrosis (2022)
  • Author(s): Ohkouchi Shinya、Kanehira Masahiko、Saigusa Daisuke、Ono Manabu、Tazawa Ryushi、Terunuma Hideya、Hirano Taizou、Numakura Tadahisa、Notsuda Hirotsugu、Inoue Chihiro、Saito-Koyama Ryoko、Tabata Masao、Irokawa Toshiya、Ogawa Hiromasa、Kurosawa Hajime、Okada Yoshinori
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: 67 Issue: 3 Pages: 320-333
  • DOI: 10.1165/rcmb.2021-0445oc
  • Peer Reviewed / Open Access
• [Journal Article] Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel (2022)
  • Author(s): Suzuki Norio、Iwamura Yuma、Nakai Taku、Kato Koichiro、Otsuki Akihito、Uruno Akira、Saigusa Daisuke、Taguchi Keiko、Suzuki Mikiko、Shimizu Ritsuko、Yumoto Akane、Okada Risa、Shirakawa Masaki、Shiba Dai、Takahashi Satoru、Suzuki Takafumi、Yamamoto Masayuki
  • Journal Title: Kidney International Volume: 101 Issue: 1 Pages: 92-105
  • DOI: 10.1016/j.kint.2021.09.031
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidic acid receptor _1/3 antagonist inhibits the activation of satellite glial cells and reduces acute nociceptive responses (2022)
  • Author(s): Hoshino Yoko、Okuno Toshiaki、Saigusa Daisuke、Kano Kuniyuki、Yamamoto Shota、Shindou Hideo、Aoki Junken、Uchida Kanji、Yokomizo Takehiko、Ito Nobuko
  • Journal Title: The FASEB Journal Volume: 36 Issue: 4
  • DOI: 10.1096/fj.202101678r
  • Peer Reviewed / Open Access
• [Journal Article] Urine autotaxin levels reflect the disease activity of sarcoidosis (2022)
  • Author(s): Murakami Koji、Tamada Tsutomu、Saigusa Daisuke、Miyauchi Eisaku、Nara Masayuki、Ichinose Masakazu、Kurano Makoto、Yatomi Yutaka、Sugiura Hisatoshi
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 4372-4372
  • DOI: 10.1038/s41598-022-08388-6
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of kit-based metabolomics with other methodologies in a large cohort, towards establishing reference values. (2021)
  • Author(s): Saigusa D*, Hishinuma E, Matsukawa N, Takahashi M, Inoue J, Tadaka S, Motoike I N, Hozawa A, Izumi Y, Bamba T, Kinoshita K, Ekroos K, Koshiba S, Yamamoto M.
  • Journal Title: Metabolites Volume: 11(10) Issue: 10 Pages: 652-652
  • DOI: 10.3390/metabo11100652
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nrf2 plays a critical role in the metabolic response during and after spaceflight (2021)
  • Author(s): Uruno A、Saigusa D、Suzuki T、Yumoto A、Nakamura T、Matsukawa N、Yamazaki T、Saito R、Taguchi K、Suzuki M、Suzuki N、Otsuki A、Katsuoka F、Hishinuma E、Okada R、Koshiba S、Tomioka Y、Shimizu R、Shirakawa M、Kensler TW.、Shiba D、Yamamoto M
  • Journal Title: Communications Biology Volume: 4 Issue: 1 Pages: 1381-1381
  • DOI: 10.1038/s42003-021-02904-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag (2021)
  • Author(s): Iwama Taiga、Kano Kuniyuki、Saigusa Daisuke、Ekroos Kim、van Echten-Deckert Gerhild、Vogt Johannes、Aoki Junken
  • Journal Title: Analytical Chemistry Volume: 93 Issue: 8 Pages: 3867-3875
  • DOI: 10.1021/acs.analchem.0c04479
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of biomarkers to diagnose diseases and find adverse drug reactions by metabolomics (2021)
  • Author(s): Saigusa Daisuke、Matsukawa Naomi、Hishinuma Eiji、Koshiba Seizo
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 37 Pages: 100373-100373
  • DOI: 10.1016/j.dmpk.2020.11.008
  • NAID: 210000172800
  • Peer Reviewed / Open Access
• [Journal Article] Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells (2021)
  • Author(s): Tamako Nishimura*, Takuya Oyama*, Hooi Ting Hu*, Toshifumi Fujioka* et al.(*:equally contributed)
  • Journal Title: Developmental Cell Volume: 56 Issue: 6 Pages: 842-859
  • DOI: 10.1016/j.devcel.2021.02.029
  • NAID: 120007172296
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 血漿およびエクソソーム由来代謝物分析手法開発と肺腺癌マーカー探索への応用 (2023)
  • Author(s): 三枝大輔、本田健、岩崎裕子、植田幸嗣、福内友子、山岡法子、副島研造、岸一馬、大熊裕介、富樫亮、松谷哲行、関順彦
  • Organizer: 第20回日本臨床腫瘍学会学術集会
• [Presentation] 宇宙環境における酸化ストレスがもたらす生体内脂質変動解析 (2022)
  • Author(s): 小池海斗、三枝大輔、宇留野晃、鈴木隆史、福内友子、山岡法子、芝大、山本雅之
  • Organizer: 第70回質量分析総合討論会
• [Presentation] UHPLC-FTMSによるヒト前房水を用いた緑内障バイオマーカー探索研究 (2022)
  • Author(s): 小暮瑞穂、佐藤孝太、藤岡周、國分太貴、吉田真彰、横山悠、福内友子、山岡法子、中澤徹、三枝大輔
  • Organizer: 第70回質量分析総合討論会
• [Presentation] 生体内メタボローム解析技術開発と疾患バイオマーカー探索研究への応用 (2022)
  • Author(s): 三枝大輔
  • Organizer: 第47回日本医用マススペクトル学会年会
• [Presentation] Lipidomic Profiling in the Large-Scale Cohort for Biomarker Discovery and the Importance of Separation Science (2022)
  • Author(s): Daisuke Saigusa
  • Organizer: Gordon Research Conference, Lipidomics
  • Int'l Joint Research / Invited
• [Presentation] 疾患関連リゾリン脂質の高精密定量を目的とした分離分析系の開発について (2021)
  • Author(s): 三枝大輔、青木淳賢
  • Organizer: 第32回クロマトグラフィー科学会議
  • Invited
• [Presentation] Addressing accuracy of reference values in a large-scale cohort by MS-based metabolomics (2021)
  • Author(s): Daisuke Saigusa
  • Organizer: VPAP
  • Int'l Joint Research / Invited
• [Presentation] Evaluation for quantified values of lipidomic profiling in a large-scale cohort (2021)
  • Author(s): Daisuke Saigusa
  • Organizer: iSLS10
  • Int'l Joint Research / Invited
• [Presentation] 質量分析イメージングの高感度検出に向けた研究 (2021)
  • Author(s): 三枝大輔、青木淳賢
  • Organizer: 第74回イオン反応研究部会講演会
  • Invited
• [Presentation] 質量分析イメージングによる疾患バイオマーカーの機能評価に関する研究 (2021)
  • Author(s): 三枝大輔
  • Organizer: 日本薬学会第141年会
  • Invited
• [Presentation] The utility of conductive adhesive film for the distribution analysis of small molecule by MALDI－MSI (2020)
  • Author(s): Daisuke Saigusa
  • Organizer: 24h-IMSI
  • Int'l Joint Research / Invited
• [Book] Mass Spectrometry for Lipidomics: Methods and Applications (2022)
  • Author(s): Michal Holcapek, Kim Ekroos
  • Total Pages: 752
  • Publisher: WILEY
  • ISBN: 9783527836505
• [Book] メタボロミクス実践ガイド (2021)
  • Author(s): 馬場 健史、平山 明由、松田 史生、津川 裕司
  • Total Pages: 334
  • Publisher: 羊土社
  • ISBN: 9784758122511