Regulation of hematopoietic and leukemic stem cells by the polycomb complexes

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390289
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Chiba University
• Principal Investigator: IWAMA Atsushi 千葉大学, 大学院・医学研究院, 教授 (70244126)
• Co-Investigator(Kenkyū-buntansha): MIYAGI Satoru 千葉大学, 大学院・医学研究院, 助教 (20400997)
• Co-Investigator(Renkei-kenkyūsha): OGURO Hideyuki 千葉大学, 大学院・医学研究院, 博士研究員 ; MOCHIZUKI Makiko (KASIO Makiko) 千葉大学, 大学院・医学研究院, 博士研究員
• Project Period (FY): 2009 – 2011
• Keywords: ポリコーム複合体 / 造血幹細胞 / 白血病幹細胞

Research Abstract

We demonstrated that the polycomb complexes function in the maintenance of multipotency of hematopoietic cells. We also showed that the polycomb complexes oncogenic exert oncogenic as well as tumor suppressor function, depending on the cellular context.

Research Products

• [Journal Article] Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes (2012)
  • Author(s): Oguro H, Yuan J, Tanaka S, Miyagi S, Mochizuki-Kashio M, Ichikawa H, Yamazaki S, Koseki H, Nakauchi H, Iwama A
  • Journal Title: J Exp Med Volume: 209 Pages: 445-454
  • Peer Reviewed
• [Journal Article] Dependency on the polycomb protein Ezh2 distinguishes fetal from adult hematopoietic stem cells (2011)
  • Author(s): Mochizuki-Kashio M, Mishima Y, Miyagi S, Negishi M, Saraya A, Konuma T, Shinga J, Koseki H, Iwama A
  • Journal Title: Blood Volume: 118 Pages: 6553-6561
  • Peer Reviewed
• [Journal Article] Non-myelinating Schwann cells in the mouse bone marrow niche maintain haematopoietic stem cell hibernation through TGF-β signaling (2011)
  • Author(s): Yamazaki S, Ema H, Karlsson G, Yamaguchi T, Miyoshi H, Shioda S, Taketo MM, Karlsson S, Iwama A, Nakauchi H
  • Journal Title: Cell Volume: 147 Pages: 1146-1158
  • Peer Reviewed
• [Journal Article] The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis (2011)
  • Author(s): Mishima Y, Miyagi S, Saraya A, Negishi M, Endoh M, Endo TA, Toyoda T, Shinga J, Katsumoto T, Chiba T, Yamaguchi N, Kitabayashi I, Koseki H, Iwama A
  • Journal Title: Blood Volume: 118 Pages: 2443-2453
  • Peer Reviewed
• [Journal Article] Bmi1 is essential for leukemic reprogramming of myeloid progenitor cells (2011)
  • Author(s): Yuan J, Takeuchi M, Negishi M, Oguro H, Ichikawa H, Iwama A
  • Journal Title: Leukemia Volume: 25 Pages: 1335-1343
  • Peer Reviewed
• [Journal Article] Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells (2011)
  • Author(s): Konuma T, Nakamura S, Miyagi S, Negishi M, Chiba T, Oguro H, Yuan J, Mochizuki-Kashio M, Ichikawa H, Miyoshi H, Vidal M Iwama A
  • Journal Title: Exp Hematol Volume: 39 Pages: 697-709
  • Peer Reviewed
• [Journal Article] Direct activation of STAT5 by ETV6-Lyn fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis (2011)
  • Author(s): Takeda Y, Nakaseko C, Tanaka H, Takeuchi M, Yui M, Saraya A, Miyagi S, Wang C, Tanaka S, Ohwada C, Sakaida E, Yamaguchi N, Yokote K, Hennighausen L, Iwama A
  • Journal Title: Br J Haematol Volume: 153 Pages: 589-598
  • Peer Reviewed
• [Journal Article] Polycomb group gene Bmi1 plays a role in the growth of thymic epithelial cells (2011)
  • Author(s): Guo Y, Miyazaki M, Itoi M, Satoh R, Iwama A, Amagai T, Kawamoto H, Kanno M
  • Journal Title: Eur J Immunol Volume: 41 Pages: 1098-1107
  • Peer Reviewed
• [Journal Article] Role of polycomb group proteins in hematopoietic stem cells (2010)
  • Author(s): Konuma T, Oguro H, Iwama A
  • Journal Title: (Review) Dev Growth Differ Volume: 52 Pages: 505-516
  • Peer Reviewed
• [Journal Article] A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/Arf locus through polycomb repressive complex 1 (2010)
  • Author(s): Negishi M, Saraya A, Mochizuki S, Helin K, Koseki H, Iwama A
  • Journal Title: PLoS ONE Volume: 5 Pages: e12373
  • Peer Reviewed
• [Journal Article] The polycomb-group gene Bmi1 promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf-dependent and independent manners (2010)
  • Author(s): Chiba T, Seki A, Aoki R, Ichikawa H, Negishi M, Miyagi S, Oguro H, Saraya A, Kamiya A, Nakauchi H, Yokosuka O, Iwama A
  • Journal Title: Hepatology Volume: 52 Pages: 1111-1123
  • Peer Reviewed
• [Journal Article] Array-based genomic resequencing of human leukemia (2010)
  • Author(s): Yamashita Y, Yuan J, Suetake I, Suzuki H, Ishikawa Y, Choi YL, Ueno T, Soda M, Hamada T, Haruta H, Takada S, Miyazaki Y, Kiyoi H, Ito E, Naoe T, Tomonaga M, Toyota M, Tajima S, Iwama A, Mano H
  • Journal Title: Oncogene Volume: 24 Pages: 3723-3731
  • Peer Reviewed
• [Journal Article] FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cells (2010)
  • Author(s): Sugawara T, Oguro H, Negishi M, Morita Y, Ichikawa H, Iseki T, Yokosuka O, Nakauchi H, Iwama A
  • Journal Title: Exp Hematol Volume: 38 Pages: 696-706
  • Peer Reviewed
• [Journal Article] Depletion of Dnmt1-associated protein 1 triggers DNA damage and compromises the proliferative capacity of hematopoietic stem cells (2010)
  • Author(s): Koizumi T, Negishi M, Nakamura S, Oguro H, Satoh K, Ichinose M, Iwama A
  • Journal Title: Int J Hematol Volume: 91 Pages: 611
  • Peer Reviewed
• [Journal Article] The polycomb-group gene product Ezh2 regulates proliferation and differentiation of murine hepatic stem/progenitor cells (2010)
  • Author(s): Aoki R, Chiba T, Miyagi S, Negishi M, Konuma T, Taniguchi H, Ogawa M, Yokosuka O, Iwama A
  • Journal Title: J Hepatology Volume: 52 Pages: 854-863
  • Peer Reviewed
• [Journal Article] Poised lineage specification in multipotent hematopoietic stem and progenitor cells by the polycomb protein Bmi1 (2010)
  • Author(s): Oguro H, Yuan J, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, Nakauchi H, Iwama A
  • Journal Title: Cell Stem Cell Volume: 6 Pages: 279-286
  • Peer Reviewed
• [Journal Article] Identification of a novel TEL-Lyn fusion gene in primary myelofibrosis (2010)
  • Author(s): Tanaka H, Takeuchi M, Takeda Y, Sakai S, Oda K, Abe D, Ohwada C, Ozawa S, Sakaida E, Shimizu N, Saito Y, Miyagi S, Iwama A, Nakaseko C
  • Journal Title: Leukemia Volume: 24 Pages: 297
  • Peer Reviewed
• [Journal Article] DMAP1 is essential for the recruitment of Pcna to repair foci (2009)
  • Author(s): Negishi M, Chiba T, Saraya A, Miyagi S, Iwama A
  • Journal Title: Genes Cells Volume: 14 Pages: 1347-1357
  • Peer Reviewed
• [Journal Article] Plk1 regulates liver tumor cell death by phosphorylation of TAp63 (2009)
  • Author(s): Komatsu S, Takenobu H, Ozaki T, Ando K, Koida N, Suenaga Y, Ichikawa T, Hishiki T, Chiba T, Iwama A, Yoshida H, Ohnuma N, Nakagawara A Kamijo T
  • Journal Title: Oncogene Volume: 28 Pages: 3631-3641
  • Peer Reviewed
• [Journal Article] (20) Tumor suppression by phospholipase C-b3 via SHP-1-mediated dephosphorylation of Stat5 (2009)
  • Author(s): Xiao W, Hong H, Kawakami Y, Kato Y, Wu D, Yasudo H, Kimura A, Kuwabara H, Bertoli LF, Davis RS, Chau LA, Madrenas J, Hsia CC, Xenocostas A, Kipps TJ, Hennighausen L
  • Journal Title: Cancer Cell Volume: 16 Pages: 161-171
  • Peer Reviewed
• [Journal Article] Cancer stem cells in hepatocellular carcinoma : recent progress and perspective (2009)
  • Author(s): Chiba T, Kamiya A, Yokosuka O, Iwama A
  • Journal Title: Cancer letters Volume: 286 Pages: 145-153
  • Peer Reviewed
• [Journal Article] Distinct expression of polycomb group proteins EZH2 and BMI1 in hepatocellular carcinoma (2009)
  • Author(s): Yonemitsu Y, Imazeki F, Chiba T, Fukai K, Nagai Y, Miyagi S, Arai M, Aoki R, Miyazaki M, Nakatani Y, Iwama A, Yokosuka O
  • Journal Title: Hum Pathology Volume: 40 Pages: 1304-1311
  • Peer Reviewed
• [Journal Article] 3-deazaneplanocin is a promising therapeutic agent for the eradication of tumor-initiating hepatocellular carcinoma cells
  • Author(s): Chiba T, Suzuki E, Negishi M, Saraya A, Miyagi S, Konuma T, Tanaka S, Tada M, Kanai F, Imazeki F, Iwama A, Yokosuka O
  • Journal Title: Int J Cancer
  • Peer Reviewed
• [Presentation] Polycomb complexes in normal and abnormal hematopoiesis (2011)
  • Author(s): Iwama A
  • Organizer: USA-Japan Cooperative Cancer Research Workshop
  • Place of Presentation: Hayama
  • Year and Date: 20110225-27
• [Presentation] 関連分野セミナー「エピジェネティクスupdate」 (2011)
  • Author(s): 岩間厚志
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] 教育講演「血液疾患とEpigenetics」 (2011)
  • Author(s): 岩間厚志
  • Organizer: 第96回近畿血液学地方会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-20
• [Presentation] 教育講演「造血器腫瘍のエピゲノム」 (2011)
  • Author(s): 岩間厚志
  • Organizer: 第73回日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] ヒト造血幹細胞の体外増幅の可能性 (2011)
  • Author(s): 岩間厚志
  • Organizer: 第21回日本サイトメトリー学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-25
• [Presentation] 造血幹細胞のエピジェネティクス (2011)
  • Author(s): 岩間厚志
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-02
• [Presentation] ワークショップ「ヒト造血幹細胞の体外増幅の可能性」 (2011)
  • Author(s): 岩間厚志
  • Organizer: 第34回日本造血細胞移植学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-02-24
• [Presentation] Regulation of hematopoietic stem cells by the polycomb repressive complexes (2010)
  • Author(s): Iwama A
  • Organizer: International conference on stem cells and cancer (ICSCC-2010)
  • Place of Presentation: Pune, India
  • Year and Date: 20101211-14
• [Presentation] 新規標的分子としてのポリコーム複合体 (2010)
  • Author(s): 岩間厚志
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20101028-30
• [Presentation] Role of the polycomb proteins in normal and cancer stem cells (2010)
  • Author(s): Iwama A
  • Organizer: The 15th Samsung International Symposium on Molecular Medicine
  • Place of Presentation: Seoul
  • Year and Date: 20101008-09
• [Presentation] ポリコーム複合体による造血幹細胞の多能性維持機構 (2010)
  • Author(s): 岩間厚志
  • Organizer: 第9回日本再生医療学会総会
  • Place of Presentation: 広島
  • Year and Date: 20100318-19
• [Presentation] Role of polycomb group proteins in the maintenance of self-renewal capacity and multipotency of hematopoietic stem cells (2010)
  • Author(s): 岩間厚志
  • Organizer: 第33回MCS23日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 新規標的分子としてのポリコーム複合体 (2009)
  • Author(s): 岩間厚志
  • Organizer: 第71回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 20091023-25
• [Presentation] 癌幹細胞のエピジェネティクスとポリコーム遺伝子 (2009)
  • Author(s): 岩間厚志
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Book] 「造血」疾患モデルマウス表現型解析指南 (2011)
  • Author(s): 指田吾郎, 岩間厚志
  • Total Pages: 248-253
  • Publisher: 中山書店,東京
• [Book] 白血病幹細胞の維持機構 (2011)
  • Author(s): 小沼貴晶, 岩間厚志
  • Total Pages: 87-95
  • Publisher: 羊土社,東京
• [Book] 造血幹細胞と再生医療 (2010)
  • Author(s): 大澤光次郎, 大津真, 岩間厚志
  • Total Pages: 113-120
  • Publisher: 羊土社,東京
• [Book] 「造血系癌幹細胞(白血病幹細胞)」「炎症・再生医学辞典」 (2009)
  • Author(s): 岩間厚志
  • Total Pages: 430-432
  • Publisher: 朝倉書店,東京
• [Book] 「白血病幹細胞」「造血器腫瘍アトラス」 (2009)
  • Author(s): 岩間厚志
  • Total Pages: 37-43
  • Publisher: 日本医事新報社,東京
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/molmed/index.html