Identification of lncRNAs during B cell lineage commitment

• Project/Area Number: 26670472
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Tomokatsu Ikawa 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 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: B細胞分化 / 長鎖ノンコーディングRNA / 造血幹細胞 / 運命決定 / エピジェネティクス

Outline of Final Research Achievements

B lymphocytes are generated from pluripotent hematopoietic stem cells (HSCs) through a successive series of lineage restriction processes. Although many transcription factors and epigenetic modifiers were found to regulate the B cell lineage commitment, the exact mechanisms were yet to be determined. We have recently established an ideal system that can be used to examine gene regulatory networks during lymphoid lineage specification from HSCs. In this study, we looked for novel long non coding (lnc) RNAs that could regulate B cell fate determination using this system. We have succeeded in identifying the lncRNAs that may be involved in the specification and commitment of HSCs toward the B cell lineage.

Research Products

• [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 / Int'l Joint Research
• [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] 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] 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 / Invited
• [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 理研 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: L'Oustau Calendal, Cassis, France
  • 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: Max Planck Institute, Freiburg, Germany
  • 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: Cold Spring Harbor Laboratory, Cold Spring Harbor, USA
  • Year and Date: 2014-04-22
• [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: 2014-04-19
  • 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/