Comprehensive analysis of splicing variants characteristic of acute myelogenous leukemia stem cells

• Project/Area Number: 21790334
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya City University (2010-2011); The Institute of Physical and Chemical Research (2009)
• Principal Investigator: KITAMURA Hiroshi 名古屋市立大学, 大学院・医学研究科, 准教授 (80312403)
• Co-Investigator(Renkei-kenkyūsha): OHARA Osamu 独立行政法人理化学研究所, 免疫アレルギー科学総合研究センター, グループディレクター (20370926) ; ISHIKAWA Fumihiko 独立行政法人理化学研究所, 免疫アレルギー科学総合研究センター, グループディレクター (30403918)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: マイクロアレイ / ゲノム / 骨髄性白血病 / 白血病幹細胞 / トランスクリプトーム / スプライシング / エクソンアレイ / 急性骨髄性白血病 / ミエロイド / 疾患関連分子 / 網羅的遺伝子発現解析 / がん幹細胞

Research Abstract

In this study, we attempted to identify genes whose exon usage is modulated in acute myelogenous leukemia(AML) stem cells. Taking advantage of Affymetrix Exon 1.0ST arrays, we evinced that 117 genes represent distinct exon usage compared with hematopoietic stem cells from healthy volunteers. In addition, total 481 transcripts showed expressional changes in AML stem cells. We also found 16 genes undergo changes in exon usage along with differentiation of AML-like cell lines. Although we failed to find genes responsible for leukemogenesis in gene transfer studies, some genes/splicing variants regulates inflammatory responses.

Research Products

• [Journal Article] SP600125 Inhibits Cap-dependent Translation Independently of the c-Jun N-terminal Kinase Pathway (2011)
  • Author(s): Masatoshi Ito, Hiroshi Kitamura, Chisato Kikuguchi, Koji Hase, Hiroshi Ohno, and Osamu Ohara
  • Journal Title: Cell Structure and Function Volume: 36 Issue: 1 Pages: 27-33
  • DOI: 10.1247/csf.10025
  • NAID: 130004137561
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed
• [Journal Article] The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells (2011)
  • Author(s): Motomura, Y., et al
  • Journal Title: Nature Immunology Volume: 12 Issue: 5 Pages: 450-459
  • DOI: 10.1038/ni.2020
  • Peer Reviewed
• [Journal Article] CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch (2011)
  • Author(s): Ebisawa, M., et al
  • Journal Title: Int.Immunol. Volume: 23 Issue: 4 Pages: 261-269
  • DOI: 10.1093/intimm/dxq478
  • Peer Reviewed
• [Journal Article] Mammalian polycomb-like Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate polycomb activity both at the Hox gene cluster and at Cdkn2a genes (2011)
  • Author(s): Xiangzhi Li, Kyo-ichi Isono, Daisuke Yamada, Takaho A. Endo, Mitsuhiro Endoh, Jun Shinga, Yoko Mizutani-Koseki, Arie P. Otte, Miguel Casanova, Hiroshi Kitamura, Takehiko Kamijo, Jafar Sharif, Osamu Ohara, Tetsuro Toyada, Bradley E. Bernstein, Neil Brockdorff, and Haruhiko Koseki
  • Journal Title: Mol. Cell. Biol Volume: 31(2) Issue: 2 Pages: 351-364
  • DOI: 10.1128/mcb.00259-10
  • Peer Reviewed
• [Journal Article] SP600125 inhibits cap-dependent translation independently of the c-Jun N-terminal kinase pathway. (2011)
  • Author(s): Masatoshi Ito, et al.
  • Journal Title: Cell Structure and Function Volume: 36 Pages: 27-33
  • Peer Reviewed
• [Journal Article] Characterization of multiple alternative forms of heterogeneous nuclear ribonucleoprotein K by phosphate-affinity electrophoresis (2010)
  • Author(s): Yayoi Kimura, Kayoko Nagata, Nobutake Suzuki, Ryo Yokoyama, Yuko Yamanaka, Hiroshi Kitamura, Hisashi Hirano, Osamu Ohara
  • Journal Title: Proteomics Volume: 10(21) Issue: 21 Pages: 3884-3895
  • DOI: 10.1002/pmic.201000349
  • Peer Reviewed
• [Journal Article] A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy (2010)
  • Author(s): Okita, K., Motohashi, S., Shinnakasu, R., Nagato, K., Yamasaki, K., Sato, Y., Kitamura, H., Hijikata, A., Yamashita, M., Shimizu, K., Fujii, S., Ohara, O., Taniguchi, M., Sakaida, I., Nakayama, T
  • Journal Title: Cancer Sci Volume: 101(11) Issue: 11 Pages: 2333-2340
  • DOI: 10.1111/j.1349-7006.2010.01696.x
  • NAID: 10027833301
  • Peer Reviewed
• [Journal Article] (2010)
  • Author(s): Yoriko Saito*, Hiroshi Kitamura*, Atsushi Hijikata, Mariko Tomizawa-Murasawa, Satoshi Tanaka, Shinsuke Takagi, Naoyuki Uchida, Nahoko Suzuki, Akiko Sone, Yuho Najima, Hidetoshi Ozawa, Atsushi Wake, Shuichi Taniguchi, Leonard D Shultz, Osamu Ohara, Fumihiko Ishikawa
  • Journal Title: Sci. Transl. Med. Volume: 2(17) Issue: 17 Pages: 17-9
  • DOI: 10.1126/scitranslmed.3000349
  • Peer Reviewed
• [Journal Article] The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut (2010)
  • Author(s): Keiichiro Suzuki, Mikako Maruya, Shimpei Kawamoto, Katarzyna Sitnik, Hiroshi Kitamura, William W. Agace, Sidnia Fagarasan
  • Journal Title: Immunity Volume: 33(1) Issue: 1 Pages: 71-83
  • DOI: 10.1016/j.immuni.2010.07.003
  • Peer Reviewed
• [Journal Article] A set of genes associated with the interferon-gamma response of lung cancerpatients undergoing alpha-galactosylceramide-pulsed dendritic cell therapy (2010)
  • Author(s): Kohsuke Okita, et al.
  • Journal Title: Cancer Science Volume: 101 Pages: 2333-2340
  • Peer Reviewed
• [Journal Article] Immunoposttranscriptomics-マクロファージ様細胞を用いた網羅的な翻訳制御解析を例に- (2010)
  • Author(s): 北村浩
  • Journal Title: 日本病態生理学会誌 Volume: 19 Pages: 39-48
• [Journal Article] Identification of therapeutic targets for quiescent chemotherapy-resistant human AML stem cells (2010)
  • Author(s): Yoriko Saito et al.
  • Journal Title: Science Translational Medicine (印刷中)
  • Peer Reviewed
• [Journal Article] M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex (2009)
  • Author(s): Koji Hase, Shunsuke Kimura, Hiroyuki Takatsu, Masumi Ohmae, Sayaka Kawano, Hiroshi Kitamura, Masatoshi Ito, Hiroshi Watarai, C. Clayton Hazelett, Charles Yeaman, Hiroshi Ohno
  • Journal Title: Nat. CellBiol Volume: 11(12) Issue: 12 Pages: 1427-1432
  • DOI: 10.1038/ncb1990
  • Peer Reviewed
• [Journal Article] Deficiency of the oxidative damage-specific DNA glycosylase NAIL1 leads to reduced germinal center B cell expansion (2009)
  • Author(s): Hiromi Mori, Rika Ouchida, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Yingqian Li, Xiang Gao, Akira Yasui, R. Stephan Lloyd, Ji-Yang Wang
  • Journal Title: DNA Repair(Amst) Volume: 8(11) Issue: 11 Pages: 1328-1332
  • DOI: 10.1016/j.dnarep.2009.08.007
  • Peer Reviewed
• [Journal Article] Mina an Il4 repressor, controls T helper type 2 bias (2009)
  • Author(s): Mariko Okamoto, Melanie Van Stry, Linda Chung, Madoka Koyanagi, Xizhang Sun, Yoshie Suzuki, Osamu Ohara, Hiroshi Kitamura, Atsushi Hijikata, Masato Kubo, Mark Bix
  • Journal Title: Nat. Immunol. Volume: 10(8) Issue: 8 Pages: 872-879
  • DOI: 10.1038/ni.1747
  • Peer Reviewed
• [Journal Article] Dentification of a novel subset of CD8+dendritic cells responsible for tolerance induction of cell-associated antigens (2009)
  • Author(s): Chun-Hong Qin, Yasunobu Miyake, Hitomi Kaise, Hiroshi Kitamura, Osamu Ohara, Masato Tanaka
  • Journal Title: J. Immunol. Volume: 182(7) Issue: 7 Pages: 4127-4136
  • DOI: 10.4049/jimmunol.0803364
  • Peer Reviewed
• [Journal Article] Naturally occurring regulatory dendritic cells regulate murine cutaneous graft-versus-host disease (2009)
  • Author(s): Kaori Sato, Kawori Eizumi, Tomohiro Fukaya, Shigeharu Fujita, Yumiko Sato, Hideaki Takagi, Mai Yamamoto, Naohide Yamashita, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Sho Yamasaki, Takashi Saito, Katsuaki Sato
  • Journal Title: Blood Volume: 113(19) Issue: 19 Pages: 4780-4789
  • DOI: 10.1182/blood-2008-10-183145
  • Peer Reviewed
• [Presentation] マクロファージの新たな機能制御分子による2型糖尿病関連分子の発現調節 (2011)
  • Author(s): 北村浩
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪府立大学(大阪府)
  • Year and Date: 2011-09-20
• [Presentation] モダンゲノミクスの成果と展望-如何に使いこなすか?- (2011)
  • Author(s): 北村浩
  • Organizer: 東海実験動物研究会2011年例会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-07-23
• [Presentation] マクロファージの新たな機能制御分子による2型糖尿病関連分子の発現調節 (2011)
  • Author(s): 北村浩、伊藤誠敏、木村俊介、嶋本良則、小林敦夫、菊口千智、岡部潤、渡会浩志、小原收、三好一郎
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Immunoposttranscriptomics:マクロファージ系細胞を用いた網羅的な翻訳制御解析を例に (2010)
  • Author(s): 北村浩
  • Organizer: 第20回病態生理学会(サテライトセミナー)
  • Place of Presentation: 奈良県立医科大学、橿原
  • Year and Date: 2010-01-22
• [Presentation] 骨髄性白血病細胞株におけるUSP2の発現および機能解析 (2009)
  • Author(s): 北村浩, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2009-12-09
• [Remarks]
  • URL: http://www.med.nagoya-cu.ac.jp/animal.dir/animalweb/dcem/index_ncu.html
• [Remarks]
  • URL: http://www.facebook.com/dcemncu
• [Patent(Industrial Property Rights)] Leukemia Stem Cell Markers (2011)
  • Inventor(s): 石川文彦、小原收、齊藤頼子、北村浩、土方敦司、小澤秀俊
  • Industrial Property Rights Holder: 理化学研究所
  • Acquisition Date: 2011-04-11
  • Overseas