Metabolomic analysis of blood cells by single-cell imaging mass spectrometry.

• Project/Area Number: 25293044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Setou Mitsutoshi 浜松医科大学, 医学部, 教授 (20302664)
• Co-Investigator(Kenkyū-buntansha): Takei Shiro 浜松医科大学, 医学部, 特任助教 (60398576) ; Nakashima Yuko 浜松医科大学, 医学部, 特任研究員 (20634760) ; Kimura Yoshishige 浜松医科大学, 医学部, 助教 (90274703) ; Shinriki Satoru 浜松医科大学, 医学部, 助教 (00583048) ; Hayasaka Hayasaka 浜松医科大学, 医学部, 助教 (90415927)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 血液 / 質量顕微鏡 / 一細胞 / 分子イメージング / 代謝物 / 血液細胞 / 一細胞解析 / 脂質

Outline of Final Research Achievements

Using matrix-assisted laser desorption/ionization imaging mass spectrometry and time-of-flight secondary ion mass spectrometry, we succeeded in single-cell imaging mass spectrometry of lipid by optimizing slide preparation for FACS-isolated blood cells and sample fixation. By single-cell imaging mass spectrometry we revealed different lipid composition in lymphocyte subsets and lipid metabolic change in breast cancer cell line, breast cancer stem cells and multiple myeloma (MM) cells. In addition we showed that palmitic acid, which was deceased in MM cells, is a potential multiple myeloma-specific drug.

Research Products

• [Journal Article] Imaging mass spectrometry detects dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia. (2016)
  • Author(s): Miyawaki S, Imai H, Hayasaka T, Masaki N, Ono H, Ochi T, Ito A, Nakatomi H, Setou M, Saito N.
  • Journal Title: Neuroscience. Volume: 322 Pages: 66-77
  • DOI: 10.1016/j.neuroscience.2016.02.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Imaging Mass Spectrometry Reveals a Unique Distribution of Triglycerides in the Abdominal Aortic Aneurysmal Wall. (2015)
  • Author(s): Tanaka H, Zaima N, Sasaki T, Yamamoto N, Inuzuka K, Sano M, Saito T, Hayasaka T, Goto-Inoue N, Sato K, Kugo H, Moriyama T, Konno H, Setou M, Unno N.
  • Journal Title: J Vasc Res Volume: 52 Issue: 2 Pages: 127-135
  • DOI: 10.1159/000439169
  • Peer Reviewed / Open Access
• [Journal Article] Direct profiling of the phospholipid composition of adult Caenorhabditis elegans using whole-body imaging mass spectrometry. (2015)
  • Author(s): Hameed S, Ikegami K, Sugiyama E, Matsushita S, Kimura Y, Hayasaka T, Sugiura Y, Masaki N, Waki M, Ohta I, Hossen MA, Setou M
  • Journal Title: Anal Bioanal Chem Volume: 407 Issue: 25 Pages: 7589-7602
  • DOI: 10.1007/s00216-015-8932-7
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut. (2015)
  • Author(s): Kunisawa J, Arita M, Hayasaka T, Harada T, Iwamoto R, Nagasawa R, Shikata S, Nagatake T, Suzuki H,Hashimoto E, Kurashima Y, Suzuki Y, Arai H, Setou M, Kiyono H.
  • Journal Title: Sci Rep. Volume: 5 Pages: 9750-9750
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: A single-cell MALDI-IMS approach. (2015)
  • Author(s): Hossen A, Nagata Y, Waki M, Ide Y, Takei S, Fukano H, Romero-Perez GA, Tajima S, Yao I, Ohnishi K,Setou M.
  • Journal Title: Anal Bioanal Chem Volume: 407 Issue: 18 Pages: 5273-80
  • DOI: 10.1007/s00216-015-8741-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Changes of Phosphatidylcholine and Fatty Acids in Germ Cells during Testicular Maturation in Three Developmental Male Morphotypes of Macrobrachium rosenbergii Revealed by Imaging Mass Spectrometry. (2015)
  • Author(s): Siangcham T, Chansela P, Hayasaka T, Masaki N, Sroyraya M, Poljaroen J, Suwansa-ard S, Attakorn, Engsusophon A, Hanna PJ, Sobhon P, Setou M.
  • Journal Title: PLoS ONE Volume: 10 Issue: 3 Pages: e0120412-e0120412
  • DOI: 10.1371/journal.pone.0120412
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Palmitic acid, verified by lipid profiling using secondary ion mass spectrometry, demonstrates anti-multiple myeloma activity. (2015)
  • Author(s): Nagata Y, Ishizaki I, Waki M, Ide Y, Hossen MA, Ohnishi K, Miyayama T, Setou M.
  • Journal Title: Leukemia Research Volume: in press Issue: 6 Pages: 638-645
  • DOI: 10.1016/j.leukres.2015.02.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease. (2014)
  • Author(s): Yuki D, Sugiura Y, Zaima N, Akatsu H, Takei S, Yao I, Maesako M, Kinoshita A, Yamamoto T, Kon R, Sugiyama K, Setou M.
  • Journal Title: Sci Rep Volume: - Issue: 1 Pages: 7130-7130
  • DOI: 10.1038/srep07130
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Single-cell time-of-flight secondary ion mass spectrometry reveals that human breast cancer stem cells have significantly lower content of palmitoleic acid compared to their counterpart non-stem cancer cells. (2014)
  • Author(s): Waki M, Ide Y, Ishizaki I, Nagata Y, Masaki N, Sugiyama E, Kurabe N, Nicolaescu D, Yamazaki F, HayasakaT, Ikegami K, Kondo T, Shibata K, Hiraide T, Taki Y, Ogura H, Shiiya N, Sanada N, Setou M.
  • Journal Title: Biochimie Volume: 107 Pages: 73-77
  • DOI: 10.1016/j.biochi.2014.10.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased phosphatidylcholine (16:0/16:0) in the folliculus lymphaticus of Warthin tumor. (2014)
  • Author(s): He Q, Takizawa Y, Hayasaka T, Noritaka M, Kusama Y, Su J, Mineta H, Setou M.
  • Journal Title: Anal Bioanal Chem Volume: 406 Issue: 24 Pages: 5815-5825
  • DOI: 10.1007/s00216-014-7890-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Application of 2,5-dihydroxyacetophenone with sublimation provides more efficientionization of lipid species by atmospheric pressure matrix-assisted laser desorption/ionization imaging mass spectrometry. (2014)
  • Author(s): Hayasaka T, Goto-Inoue N, Masaki N, Ikegami K, Setou M.
  • Journal Title: Surf Interface Anal Volume: 46 Issue: 12-13 Pages: 1219-1222
  • DOI: 10.1002/sia.5592
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Single Cell Lipidomics of SKBR-3 Breast Cancer Cells by Using Time-of-Flight Secondary-Ion Mass Spectrometry. (2014)
  • Author(s): Ide Y, Waki M, Ishizaki I, Nagata Y, Yamazaki F, Hayasaka T, Masaki N, Ikegami K, Kondo T, Shibata K, Ogura H, Sanada N, Setou M.
  • Journal Title: Surf Interface Anal. Volume: in press
  • Peer Reviewed
• [Presentation] マスイメージングが明らかにする脂質の分布とその意義 (2016)
  • Author(s): 瀬藤 光利
  • Organizer: 日本化学会第96春季年会（2016）
  • Place of Presentation: 同志社大学 京田辺キャンパス（京都府・京田辺市）
  • Year and Date: 2016-03-24
  • Invited
• [Presentation] Platform of functional metabolic imaging (2016)
  • Author(s): 瀬藤 光利
  • Organizer: 日独国際ワークショップ
  • Place of Presentation: Tubingen（Germany）
  • Year and Date: 2016-03-21
  • Int'l Joint Research / Invited
• [Presentation] Development and application of imaging mass spectrometry (2016)
  • Author(s): 瀬藤 光利
  • Organizer: 第8回NAGOYAグローバルリトリート
  • Place of Presentation: あいち健康プラザ（愛知県・名古屋市）
  • Year and Date: 2016-02-12
  • Invited
• [Presentation] Single cell lipidomics approach for diseases (2015)
  • Author(s): 瀬藤 光利
  • Organizer: Biochemistry and Molecular Biology 2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] リポクオリティの可視化 (2015)
  • Author(s): 瀬藤 光利
  • Organizer: 第9回メタボロームシンポジウム
  • Place of Presentation: 三島市民文化会館（静岡県・三島市）
  • Year and Date: 2015-09-30
  • Invited
• [Presentation] Three-Dimensional Image of Cleavage Bodies in Nuclei Is Configured Using Gas Cluster Ion Beam with Time-of-Flight Secondary Ion Mass Spectrometry (2015)
  • Author(s): 正木 紀隆
  • Organizer: SISS-17
  • Place of Presentation: 成蹊大学（東京都・武蔵野市）
  • Year and Date: 2015-06-26
  • Int'l Joint Research
• [Presentation] ガスクラスターイオンビームと飛行時間型二次イオン質量分析を組み合わせた核内三次元構造解析 (2015)
  • Author(s): 正木 紀隆
  • Organizer: 医学生物学電子顕微鏡技術学会第31回学術講演会
  • Place of Presentation: 名古屋市立大学（愛知県・名古屋市）
  • Year and Date: 2015-06-21
• [Presentation] 質量顕微鏡の開発と応用 (2015)
  • Author(s): 瀬藤 光利
  • Organizer: 日本顕微鏡学会平成27年総会
  • Place of Presentation: 京都国際会館（京都府・京都市）
  • Year and Date: 2015-05-14
  • Invited
• [Presentation] Three-Dimensional Image of Cleavage Bodies in Nuclei Is Configured with Gas Cluster Ion Beam/Time-of-Flight Secondary Ion Mass Spectrometry (2015)
  • Author(s): Mitsutoshi Setou
  • Organizer: 9th Asian Biophysics Association
  • Place of Presentation: Shaoxing(China）
  • Year and Date: 2015-05-10
  • Int'l Joint Research
• [Presentation] Single cell MALDI-IMS outlines that PC(34:1) is downregulated in multiple myeloma cell compared to normal plasma cells (2014)
  • Author(s): Hossen Md Amir, Yasuyuki Nagata, Michihiko Waki, Yoshimi Ide, Kazunori Ohnishi, Mitsutoshi Setou
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 質量顕微鏡の開発と応用 (2014)
  • Author(s): 瀬藤光利
  • Organizer: 第32回日本ヒト細胞学会学術集会
  • Place of Presentation: 東京慈恵会医科大学（東京都港区）
  • Year and Date: 2014-08-30 – 2014-08-31
  • Invited
• [Presentation] Cellular imaging mass specrrometory of lipids (2014)
  • Author(s): Mitsutoshi Setou
  • Organizer: EMBO WORK SHOP
  • Place of Presentation: Aequa Hotel(Vico Equense, Italy)
  • Year and Date: 2014-06-02 – 2014-06-06
  • Invited
• [Presentation] Potentiality of MALDI-IMS to analyze PC at hematopoietic single cell level. (2014)
  • Author(s): Hossen, Md Amir, Yasuyuki Nagata, Michihiko Waki, Yoshimi Ide and Mitsutoshi Setou
  • Organizer: 第62回質量分析総合討論会
  • Place of Presentation: ホテル阪急エキスポパーク（大阪）
  • Year and Date: 2014-05-14 – 2014-05-16
• [Presentation] Application of Imaging Mass Spectrometry for Biological Samples (2013)
  • Author(s): Takahiro Hayasaka
  • Organizer: 9th International Symposium on Atomic Level Characterizations for New Materials and Devices’13
  • Place of Presentation: Sheraton Kona（Hawaii, USA）
  • Invited
• [Presentation] Lipid imaging with mass spectrometry (2013)
  • Author(s): Mitsutoshi Setou
  • Organizer: 16th GEM - 10th GERLI meeting - GEM/GERLI lipidomics meeting
  • Place of Presentation: Saint-Jean-Cap-Ferrat(France)
  • Invited
• [Presentation] Subcellular analysis using TOF-SIMS successfully depicts organelles in nuclei (2013)
  • Author(s): Mitsutoshi Setou
  • Organizer: 19th international conference on secondary ion mass spectrometry (SIMS-19)
  • Place of Presentation: ICC JEJU(Korea)
• [Presentation] Single Cell Analysis of Multiple Myeloma With Secondary Ion Mass Spectrometry (2013)
  • Author(s): Yoshiyuki Nagata, Itsuko Ishizaki, Yoshimi Ide, Michihiko Waki, Kazunori Ohnishi, Noriaki Sanada and Mitsutoshi Setou
  • Organizer: 19th International Conference on Secondary Ion Mass Spectrometry
  • Place of Presentation: ICC JEJU(Korea)
• [Presentation] Single-Cell Analysis of Human Breast Cancer Cells by Secondary-Ion Mass Spectrometry (2013)
  • Author(s): Yoshimi Ide, Michihiko Waki,Itsuko Ishizaki, Yasuyuki Nagata, Hiroyuki Ogura, Noriaki Sanada and Mitsutoshi Setou
  • Organizer: 19th International Conference on Secondary Ion Mass Spectrometry
  • Place of Presentation: ICC JEJU(Korea)
• [Presentation] 創薬における質量顕微鏡法の可能性 (2013)
  • Author(s): 瀬藤光利
  • Organizer: 創薬薬理フォーラム 第21回シンポジウム
  • Place of Presentation: 日本薬学会 長井記念館 （東京都渋谷区）
• [Presentation] IMAGING MASS SPECTROMETRY WITH ION MOBILITY (2013)
  • Author(s): Mitsutoshi Setou
  • Organizer: Translating Omics Science to Clinical Applications 2013 (TOSCA'13)
  • Place of Presentation: City University of Hong Kong, Hong Kong
  • Invited
• [Presentation] Imaging mass spectrometry of lipids. (2013)
  • Author(s): Mitsutoshi Setou
  • Organizer: Federation of American Societies for Experimental Biology Science Research Conferences(FASEB SRC)
  • Place of Presentation: ニセコヒルトンホテル（北海道ニセコ）
  • Invited
• [Presentation] 質量顕微鏡研究とトランスレーショナルリサーチャー (2013)
  • Author(s): 瀬藤光利
  • Organizer: 第21回日本乳癌学会学術総会
  • Place of Presentation: アクトシティ浜松（浜松）
• [Presentation] Development and Application of Imaging Mass Spectrometry (2013)
  • Author(s): 瀬藤光利
  • Organizer: RJG-Ph.D. Congress XIV
  • Place of Presentation: Jomtien Palm Beach Resort（Thai）
  • Invited
• [Presentation] 細胞・組織の２Ｄ質量分析イメージング
  • Author(s): 瀬藤光利
  • Organizer: 日本学術会議公開シンポジウム「医学・生命科学の革新的発展に資する統合バイオイメージングの展望 」
  • Place of Presentation: 日本学術会議講堂(東京都港区)
  • Invited
• [Remarks] 国立大学法人 浜松医科大学 解剖学講座 細胞生物学分野
  • URL: http://www.hama-med.ac.jp/mt/setou/ja/
• [Remarks] 浜松医科大学 解剖学講座 細胞生物学分野
  • URL: http://www.hama-med.ac.jp/mt/setou/ja/
• [Patent(Industrial Property Rights)] 骨髄腫細胞死誘導剤及びこれを含有する骨髄腫治療用医薬組成物 (2014)
  • Inventor(s): 瀬藤光利、永田泰之
  • Industrial Property Rights Holder: 浜松医科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-087394
  • Filing Date: 2014-04-21