Roles of metabolic regulation in B cell fate determination

• Project/Area Number: 26293229
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ikawa Tomokatsu 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (60450392)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: B細胞 / 運命決定 / 代謝 / 造血幹細胞 / 分化 / B細胞分化 / 細胞内代謝 / インスリン / 転写因子

Outline of Final Research Achievements

All hematpoietic / immune cells including B cells are generated from hematopoietic stem cells(HSCs). HSCs gradually specify their differentiation potential to finally commit to the B cell lineage. Although transcription factors (TFs) are shown to be essential for the cell fate decision, the roles of the TFs in regulating cellular metabolisms remain to be determined. We have recently established a culture system to examine the molecular mechanisms of B cell fate determination. Using this sytem, we demonstrated that the insulin signals are important for early B cell differentiation.

Research Products

• [Journal Article] Kelch-like protein 14 promotes B-1a but suppresses B-1b cell development. (2018)
  • Author(s): Li S, Liu J, Min Q, Ikawa T, Yasuda S, Yang Y, Wang YQ, Tsubata T, Zhao Y, Wang JY.
  • Journal Title: Int Immunol Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells. (2018)
  • Author(s): Miyai T, Takano J, Endo TA, Kawakami E, Agata Y, Motomura Y, Kubo M, Kashima Y, Suzuki Y, Kawamoto H, Ikawa T.
  • Journal Title: Genes Dev Volume: 32 Pages: 112-126
  • Peer Reviewed
• [Journal Article] CAGE profiles of human and mouse samples. (2017)
  • Author(s): Noguchi S, Arakawa T,…, Ikawa T (75 out of 178),…, Kawaji H*, Carninci P, Forrest ARR, Hayashizaki Y.
  • Journal Title: Sci Data Volume: 4 Pages: 170112-170112
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program (2016)
  • Author(s): Ikawa T, Masuda K, Endo TA, Endo M, Isono K, Koseki Y, Nakagawa R, Kometani K, Takano J, Agata Y, Katsura Y, Kurosaki T, Vidal M, Koseki H, Kawamoto H
  • Journal Title: Genes & Development Volume: 30 Pages: 2475-2485
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Transient Tcf3 gene repression by TALE-tanscription factor targeting (2016)
  • Author(s): 2.Masuda J, Kawamoto H, Strober W, Takayama-E, Mizutani A, Murakami H, Ikawa T, Kitani A, Maeno N, Shigehiro T, Satoh A, Seno A, Arun V, Kasai T, Fuss IJ, Katsura Y, Seno M
  • Journal Title: Appl Biochem Biotechnol Volume: 36 Pages: 1559-1573
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of Polycomb RYBP in maintaining the B-1 to B-2 B-cell lineage switch in adult hematopoiesis (2015)
  • Author(s): Cales C, Pavon L, Starowicz K, Perrez C, Bravo M, Ikawa T, Koseki H, Vidal M
  • Journal Title: Mol Cell Biol. Volume: 36 Issue: 6 Pages: 900-912
  • DOI: 10.1128/mcb.00869-15
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Induced developmental arrest of early hematopoietic progenitors leads to the generation of leukocyte stem cells (2015)
  • Author(s): Ikawa T, Masuda K, Huijskens MJAJ, Satoh R, Kakugawa K, Agata Y, Miyai T, Germeraad WTV, Katsura Y, Kawamoto H
  • Journal Title: Stem Cell Reports Volume: 5 Pages: 716-727
  • NAID: 120005745636
  • Peer Reviewed / Open Access
• [Journal Article] CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability. (2015)
  • Author(s): Takeshi Inoue, Masahiro Morita, Atsushi Hijikata, Yoko Fukuda-Yuzawa, Shungo Adachi, Kyoichi Isono, Tomokatsu Ikawa, Hiroshi Kawamoto, Haruhiko Koseki, Tohru Natsume, Taro Fukao, Osamu Ohara, Tadashi Yamamoto, Tomohiro Kurosaki
  • Journal Title: Journal of Experimental Medicine Volume: 212 Issue: 9 Pages: 1465-1479
  • DOI: 10.1084/jem.20150384
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] BTB-ZF Protein Znf131 Regulates Cell Growth of Developing and Mature T Cells. (2015)
  • Author(s): Iguchi T, Aoki K, Ikawa T, Taoka M, Taya C, Yoshitani H, Toma-Hirano M, Koiwai O, Isobe T, Kawamoto H, Masai H, Miyatake S.
  • Journal Title: The Journal of Immunology Volume: 195 Issue: 3 Pages: 982-93
  • DOI: 10.4049/jimmunol.1500602
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Gene regulation. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells (2015)
  • Author(s): Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drabløs F, Lennartsson A, Rönnerblad M, Hrydziuszko O, Vitezic M, Freeman TC, Alhendi AM, Arner P, Axton R, Baillie JK, Beckhouse A, Bodega B, Briggs J, Brombacher F, Davis M, Detmar M, Ehrlund A, Endoh M, Eslami A, Fagiolini M, et al.
  • Journal Title: Science Volume: 347 Issue: 6225 Pages: 1010-1014
  • DOI: 10.1126/science.1259418
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The transcription repressors Bach2 and Bach1 promote B cell development by repressing myeloid program. (2014)
  • Author(s): Itoh-Nakadai A, Hikota R, Muto A, Kometani K, Matsui-Watanabe M, Sato Y, Kobayashi M, Nakamura A, Miura Y, Yano Y, Tashiro S, Sun J, Ikawa T, Ochiai K, Kurosaki T, and Igarashi K.
  • Journal Title: Nature Immunol. Volume: 15 Issue: 12 Pages: 1171-1180
  • DOI: 10.1038/ni.3024
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. (2014)
  • Author(s): Hojyo S., T. Miyai, H. Fujishiro, M. Kawamura, T. Yasuda, A. Hijikata, B-H Bin, T. Irie, J. Tanaka, T. Atsumi, M. Murakami, M. Nakayama, O. Ohara, S. Himeno, H. Yoshida, H. Koseki, T. Ikawa, K. Mishima, and T. Fukada.
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Issue: 32 Pages: 11786-11791
  • DOI: 10.1073/pnas.1323557111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development (2014)
  • Author(s): Miyai T, Hojyo S, Ikawa T, Kawamura M, Irie T, Ogura H, Hijikata A, Bin BH, Yasuda T, Kitamura H, Nakayama M, Ohara O, Yoshida H, Koseki H, Mishima K, Fukada T
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 111 Issue: 32 Pages: 11780-11785
  • DOI: 10.1073/pnas.1323549111
  • Peer Reviewed / Open Access
• [Journal Article] Genetic and epigenetic control of early lymphocyte development (2014)
  • Author(s): Ikawa T
  • Journal Title: Curr Top Microbiol Immunol. Volume: 381 Pages: 1-20
  • DOI: 10.1007/82_2014_370
  • ISBN: 9783319073941, 9783319073958
  • Open Access / Acknowledgement Compliant
• [Journal Article] The epigenetic regulator Uhrf1 facilitates proliferation and maturation of colonic regulatory T cells (2014)
  • Author(s): Yuuki Obata*, Yukihiro Furusawa*, Takaho A. Endo, Jafar Sharif, Daisuke Takahashi, Koji Atarashi, Manabu Nakayama, Satoshi Onawa, Yumiko Fujimura, Masumi Takahashi, Tomokatsu Ikawa, Takeshi Otsubo, Yuki I. Kawamura, Taeko Dohi, Shoji Tajima, Osamu Ohara, Kenya Honda, Shohei Hori, Hiroshi Ohno, Haruhiko Koseki and Koji Hase. 【* : 筆頭筆者】
  • Journal Title: Nature Immunology Volume: 15 Issue: 6 Pages: 571-579
  • DOI: 10.1038/ni.2886
  • Peer Reviewed / Open Access
• [Presentation] Immunosystem development (2017)
  • Author(s): Ikawa T
  • Organizer: 日本免疫学会
  • Int'l Joint Research / Invited
• [Presentation] Three-step transcriptional priming that drives multipotent progenitors toward B cells (2017)
  • Author(s): Ikawa T, Miyai T, Takano J
  • Organizer: 日本免疫学会
  • Int'l Joint Research / Invited
• [Presentation] Epigenetic maintenance of T cell identity by Polycomb-mediated suppression of Pax5 (2017)
  • Author(s): Ikawa T
  • Organizer: BMB2017
  • Int'l Joint Research / Invited
• [Presentation] リンパ球分化とエピジェネティクス (2017)
  • Author(s): Ikawa T
  • Organizer: 大阪大学 微研・部員会共催セミナー
  • Invited
• [Presentation] A road map that guides the development of B cells. (2017)
  • Author(s): Ikawa T, Miyai T and Takano J
  • Organizer: The 3rd Tsinghua-RIKEN Joint Symposium
  • Int'l Joint Research / Invited
• [Presentation] Transcriptional networks during B lymphocyte commitment. (2017)
  • Author(s): Ikawa T, Miyai T and Takano J
  • Organizer: FASEB meeting
  • Int'l Joint Research
• [Presentation] A critical role of non-canonical PRC1 for specification to lymphoid lineage (2017)
  • Author(s): Tomokatsu Ikawa
  • Organizer: KTCC 2017
  • Place of Presentation: 京都市 京都大学
  • Int'l Joint Research
• [Presentation] Identification of gene regulatory networks during hematopoietic stem cell differentiation by the single-cell analysis (2016)
  • Author(s): Tomokatsu Ikawa
  • Organizer: Single cell Workshop2016
  • Place of Presentation: 吹田市 理研QBiC
  • Year and Date: 2016-02-24
  • Int'l Joint Research
• [Presentation] Gene regulatory networks that orchestrate T and B lymphocyte development (2016)
  • Author(s): Tomokatsu Ikawa
  • Organizer: Liaison Laboratory seminar
  • Place of Presentation: 熊本市 熊本大学
  • Year and Date: 2016-02-10
  • Invited
• [Presentation] 異性型ポリコーム複合体による造血幹細胞分化制御 (2016)
  • Author(s): 伊川 友活
  • Organizer: さきがけ終了領域報告会
  • Place of Presentation: 福岡市 九州大学
• [Presentation] Dynamic transcriptional cascades and epigenetic regulation that orchestrate B cell fate determination (2016)
  • Author(s): Junichro Takano, Tomohiro Miyai, Tomokatsu Ikawa
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 宜野湾市 沖縄コンベンションセンター
  • Int'l Joint Research
• [Presentation] Dynamic transcriptional cascades that orchestrate B cell fate determination (2016)
  • Author(s): Junichiro Takano, Tomohiro Miyai, Haruhiko Koseki, Tomokatsu Ikawa
  • Organizer: 日本血液学会学術集会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Int'l Joint Research
• [Presentation] Transcriptional networks that establish B cell identity (2016)
  • Author(s): Tomokatsu Ikawa
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne, Melbourne Convention and Exhibition Centre
  • Int'l Joint Research
• [Presentation] 異性型Polycomb repressive complex1は造血幹細胞からリンパ球系列への運命決定に重要である (2016)
  • Author(s): 高野淳一郎、古関明彦、伊川友活
  • Organizer: 第26回KTCC
  • Place of Presentation: 京都市 延暦寺会館
• [Presentation] Transcriptional regulatory networks that regulate B cell fate determination (2016)
  • Author(s): Tomokatsu Ikawa
  • Organizer: CSHL meeting
  • Place of Presentation: Cold Spring Harbor, Cold Spring Harbor Laboratory
  • Int'l Joint Research
• [Presentation] Transcriptional networks that control B cell fate determination (2015)
  • Author(s): Tomokatsu Ikawa
  • Organizer: BMB2015
  • Place of Presentation: 神戸市 神戸国際展示場
  • Year and Date: 2015-12-02
  • Int'l Joint Research / Invited
• [Presentation] Role of IRS-1 in early B cell development (2015)
  • Author(s): Tomokatsu Ikawa
  • Organizer: 日本免疫学会2015
  • Place of Presentation: 札幌市 札幌コンベンションセンター
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] Epigenetic maintenance of T cell fate by Polycomb group proteins (2015)
  • Author(s): Tomokatsu Ikawa
  • Organizer: 内藤カンファレンス
  • Place of Presentation: 札幌市 シャトレーゼ ガトーキングダムサッポロ
  • Year and Date: 2015-09-15
  • Int'l Joint Research
• [Presentation] B細胞系列への運命決定過程における転写制御ネットワークの解明 (2015)
  • Author(s): 宮井智浩、伊川友活
  • Organizer: KTCC
  • Place of Presentation: 京都 京都大学芝蘭会館
  • Year and Date: 2015-05-15
• [Presentation] Gene regulatory network orchestrating B cell fate specification (2015)
  • Author(s): Tomokatsu Ikawa
  • Organizer: RIKEN EPIGENETICS in Kobe
  • Place of Presentation: 神戸市 RIKEN CDB
  • Year and Date: 2015-02-13
• [Presentation] Epigenetic maintenance of T cell identity by Polycomb-mediated suppression of Pax5 (2014)
  • Author(s): Tomokatsu Ikawa
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都市 国立京都国際会館
  • Year and Date: 2014-12-11
• [Presentation] T細胞系列への運命決定とエピジェネティクス (2014)
  • Author(s): 伊川 友活
  • Organizer: LEGENDセミナー
  • Place of Presentation: 京都市 ホテルグランヴィア京都
  • Year and Date: 2014-12-09
  • Invited
• [Presentation] Maintenance of T cell identity by Polycomb group proteins (2014)
  • Author(s): Ikawa T
  • Organizer: France-Japan Immunology meeting
  • Place of Presentation: フランス カシス
  • Year and Date: 2014-10-23
  • Invited
• [Presentation] Genetic and epigenetic control of early lymphocyte development (2014)
  • Author(s): Ikawa T
  • Organizer: Max Planck Institute seminar
  • Place of Presentation: ドイツ フライブルグ
  • Year and Date: 2014-10-20
  • Invited
• [Presentation] Polycomb group proteins Ring1A/B are required for the maintenance of T cell fate (2014)
  • Author(s): Ikawa T
  • Organizer: CSHL meeting
  • Place of Presentation: アメリカ コールドスプリングハーバー
  • Year and Date: 2014-04-22
  • Invited
• [Presentation] 細胞分化の研究に魅せられて (2014)
  • Author(s): 伊川 友活
  • Organizer: 新学術領域「細胞運命制御」若手の会
  • Place of Presentation: 浜松市 浜名湖ロイヤルホテル
  • Year and Date: 2014-04-22
  • Invited
• [Remarks] 多能前駆細胞を無限に増幅させる方法を開発
  • URL: http://www.riken.jp/pr/press/2015/20151023_1/