Expansion of hematopoietic stem/progenitor cells by suppressing E2A activities

2011 Fiscal Year Final Research Report

• Project/Area Number: 21689027
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: IKAWA Tomokatsu 独立行政法人理化学研究所, 免疫発生研究チーム, 研究員 (60450392)
• Project Period (FY): 2009 – 2011
• Keywords: 造血幹細胞 / 自己複製 / Id3 / 転写因子 / E2A / B細胞分化

Research Abstract

We have developed a novel method for expanding hematopoietic stem/progenitor cells by suppressing E2A activities. This was done by ectopic expression of Id3 into hematopoietic stem cells and cultured the infected cells in a B cell differentiating conditions. The cells have potential to proliferate enormously in vitro and to generate lymphoid and myeloid lineage cells. We named the cells induced Leukocyte Stem(iLS) cells.

Research Products

• [Journal Article] Notch-Hes1 pathway is required for the development of IL-17-producing gd T cells (2011)
  • Author(s): Shibata K, Yamada H, Sato T, Dejima T, Nakamura M, Ikawa T, Hara H, Yamasaki S, Kageyama R, Iwakura Y, Kawamoto H, Toh H, Yoshikai Y.
  • Journal Title: Blood Volume: 118 Pages: 586-593
  • Peer Reviewed
• [Journal Article] An essential developmental checkpoint for production of the T cell lineage (2010)
  • Author(s): Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R, Shibano-Satoh A, Kominami R, Katsura Y, and Kawamoto H.
  • Journal Title: Science Volume: 329 Pages: 93-96
  • Peer Reviewed
• [Journal Article] A map for lineage restriction of progenitors during hematopoiesis : the essence of the myeloid-based model (2010)
  • Author(s): Kawamoto H, Ikawa T, Masuda K, Wada H and Katsura Y.
  • Journal Title: Immunol Rev Volume: 238 Pages: 23-26
  • Peer Reviewed
• [Journal Article] Aberrant induction of LMO2 theE2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t (2010)
  • Author(s): Hirose K, Inukai T, Kikuchi J, Furukawa Y, Ikawa T, Kawamoto H, Oram SH, Gottgen B, Kiyokawa N, Miyagawa Y, Okita H, Akahane K, Zhang X, Kuroda I, Nonna H, Kagami K, Goi K, Kurosawa H, Look AT, Matsui H, Inaba T and Sugita K.
  • Journal Title: Blood Volume: 116 Pages: 962-970
  • Peer Reviewed
• [Journal Article] Poised lineage specification in multipotent hematopoietic progenitor cells by the polycomb protein Bmi1 (2010)
  • Author(s): Oguro H, Jin Y, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, Nakauchi H, and Iwama A.
  • Journal Title: Cell Stem Cell Volume: 6 Pages: 279-286
  • Peer Reviewed
• [Journal Article] Innate production of Th2 cytokines by adipose tissue-associated c-Kit(+) Sca-1(+) lymphocytes (2010)
  • Author(s): Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Fujiwara J-I, Ohtani M, Fujii H, and Koyasu S.
  • Journal Title: Nature Volume: 463 Pages: 540-544
  • Peer Reviewed
• [Journal Article] Direct hematological toxicity and illegitimate chromosomal recombination caused by the systemic activation of CreERT2 (2009)
  • Author(s): Higashi AY, Ikawa T, Muramatsu M, Ecnomides AN, Niwa A, Okuda T, Murphy AJ, Rojas J, Heike T, Nakahata T, Kawamoto H, Kita T, and Yanagita M.
  • Journal Title: J. Immunol. Volume: 182 Pages: 5633-5640
  • Peer Reviewed
• [Journal Article] Notch activation in thymic epithelial cells induces development of thymic microenvironments (2009)
  • Author(s): Masuda K, Germeraad WTV, Satoh R, Itoi M, Ikawa T, Minato M, Katsura Y, W. van Ewijk, and Kawamoto H.
  • Journal Title: Mol. Immunol Volume: 46 Pages: 1756-1767
  • Peer Reviewed
• [Journal Article] Lipid-mediated presentation of MHC class II molecules guides thymocytes to the CD4 lineage (2009)
  • Author(s): Komaniwa S, Hayashi H, Kawamoto H, Ikawa T, Sato SB, Katsura Y, and Udaka K.
  • Journal Title: Eur. J. Immunol Volume: 39 Pages: 96-122
  • Peer Reviewed
• [Presentation] Dissection of genetic programs during the T cell lineage specification process (2011)
  • Author(s): Ikawa T.
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] T細胞からB細胞へのリプログラミング (2011)
  • Author(s): 伊川友活
  • Organizer: 第17回血液科学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2011-11-06
• [Presentation] T細胞系列への決定における遺伝子制御ネットワークの解析 (2011)
  • Author(s): 伊川友活
  • Organizer: Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2011-06-10
• [Presentation] T細胞系列への運命決定を制御する分子機構 (2011)
  • Author(s): 伊川友活
  • Organizer: 第20回東京免疫フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2011-02-22
• [Presentation] 転写因子Bcl11bによるT細胞系列への運命決定(招待講演) (2010)
  • Author(s): 伊川友活
  • Organizer: 第114回小児血液腫瘍懇話会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-29
• [Presentation] An essential checkpoint for production of the T cell lineage (2010)
  • Author(s): Ikawa T.
  • Organizer: Inernatinal Congress of Immunology
  • Place of Presentation: 兵庫
  • Year and Date: 2010-08-24
• [Presentation] T細胞系列への決定は転写因子Bcl11bによって制御されている (2010)
  • Author(s): 伊川友活
  • Organizer: Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2010-06-04
• [Presentation] (2010)
  • Author(s): Ikawa T
  • Organizer: An essential developmental checkpoint for early T cell development CSHL meeting
  • Place of Presentation: ニューヨーク
  • Year and Date: 2010-04-22
• [Presentation] Eタンパク質機能阻害による造血幹・前駆細胞の自己複製能の誘導 (2009)
  • Author(s): 伊川友活
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] Expansion of hematopoietic stem/progenitor cells by suppressing E-protein activities (2009)
  • Author(s): Ikawa T.
  • Organizer: Transcriptional Mechanisms of Early Lymphocyte Development Symposium
  • Place of Presentation: サンディエゴ
  • Year and Date: 2009-11-05
• [Presentation] Induction of T cell development by the immobilized Notch ligand in the absence of stromal cells (2009)
  • Author(s): Ikawa T.
  • Organizer: Kyoto T cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2009-06-02
• [Patent(Industrial Property Rights)] 造血幹/前駆細胞の特性を有するB前駆細胞の製造方法 (2008)
  • Inventor(s): 河本宏、伊川友活、桂義元
  • Industrial Property Rights Holder: 桂義元
  • Industrial Property Number: 特許、特願2008-061542
  • Filing Date: 2008-03-11