Clarification of whole scheme of developmental pathway in hematopiesis by fate mapping using a genetic marking system

• Project/Area Number: 21390297
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KAWAMOTO Hiroshi 独立行政法人理化学研究所, 免疫発生研究チーム, チームリーダー (00343228)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 造血 / 前駆細胞 / 系列決定 / T細胞 / ミエロイド系細胞 / 細胞分化 / T前駆細胞 / Notchシグナル / フェイトマッピング / Bcl11b / Bclllb / B前駆細胞

Research Abstract

We have previously proposed a model of hematopoiesis in which myeloid potential is retained along with development towards T, B and erythroid lineages. In this research project, we aimed to validate this model. Validation of myeloid-B progenitors in fetal hematopoiesis by a single cell analysis was completed(to be submitted). Validation of myeloid-T progenitor stage was achieved by fixing myeloid-T progenitors using a developmental arrest-inducing culture system(Ikawa et al, Science, 2010). Fate map approaches using genetic marking mouse have not yet completed, but a useful line(Flt3-ER-Cre mouse) has been successfully made, and preliminary experiment has provided some promising data. Collectively, the project has been very successful.

Research Products

• [Journal Article] Notch-Hes1 pathway is required for the development of IL-17-producingγδT 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] Notch-Hes1 pathway is required for the development of IL-17-producing Yδ T cells (2011)
  • Author(s): K.Shibata
  • Journal Title: Blood Volume: 118 Issue: 3 Pages: 586-593
  • DOI: 10.1182/blood-2011-02-334995
  • 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 Issue: 4 Pages: 1098-1107
  • DOI: 10.1002/eji.201040794
  • Peer Reviewed
• [Journal Article] The role of the basic helix-loop-helix transcription factor Dec1 in the regulatory T cells (2010)
  • Author(s): Miyazaki K, Miyazaki M, Guo Y, Yamasaki N, Kanno M, Honda Z, Oda H, Kawamoto H, Honda H
  • Journal Title: J. ImmunolK Volume: 185 Pages: 7330-7339
  • Peer Reviewed
• [Journal Article] An essential developmental checkpoint for production of the T cell lineage (2010)
  • Author(s): Ikawa, T, S Hirose, K Masuda, K Kakugawa, R Satoh, A Shibano-Satoh, R Kominami, Y Katsura, H Kawamoto
  • Journal Title: Science Volume: 329 Pages: 93-96
  • NAID: 40018275930
  • Peer Reviewed
• [Journal Article] Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17 ; 19) (2010)
  • Author(s): Hirose K, T Inukai, J Kikuchi, Y Furukawa, T Ikawa, H Kawamoto, S H Oram, B Gottgens, N Kiyokawa, Y Miyagawa, H Okita, KAkahane, X Zhang, I Kuroda, H Honna, K Kagami, K Goi, Hu Kurosawa, A T Look, H Matsui, T Inaba, Kanji Sugita
  • Journal Title: Blood Volume: 116 Pages: 962-970
  • Peer Reviewed
• [Journal Article] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation (2010)
  • Author(s): Y. Nishikawa, F. Hirota, M. Yano, H. Kitajima, J. Miyazaki, H. Kawamoto, Y. Mouri, and M. Matsumoto
  • Journal Title: J. Exp. Med. Volume: 207 Pages: 963-971
  • Peer Reviewed
• [Journal Article] Poised lineage specification in multipotent hematopoietic progenitor cells by the polycomb protein Bmi1 (2010)
  • Author(s): Oguro H, Y Jin, H Ichikawa, T Ikawa, S Yamazaki, H Kawamoto, H Nakauchi, A Iwama
  • Journal Title: Cell Stem Cell Volume: 5 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., T. Yamada, M. Tanabe, T. Takeuchi, T. Ikawa, H. Kawamoto, J-I. Furusawa, M. Ohtani, H. Fujii, and S. Koyasu
  • Journal Title: Nature Volume: 463 Pages: 540-544
  • Peer Reviewed
• [Journal Article] In vitro human G-CSF mobilized CD34+derived T-cell progenitors fully mature in vivo (2010)
  • Author(s): Meek B, Cloosen S, Borsotti C, Elssen J V, Vanderlocht J, Schnijderberg M, Poel M van der, Leewis B, Hesselink R, Manz M G, Katsura Y, Kawamoto H, Germeraad W TV, and Bos G MJ
  • Journal Title: Blood Volume: 115 Pages: 261-264
  • Peer Reviewed
• [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Vα14-Jα18 TCRαgene (2010)
  • Author(s): Watarai H, A Rybouchkin, N Hongo, Y Nagata, S Sakata, E Sekine, N Dashtsoodol, T Tashiro, S-I Fujii, K Shimizu, K Mori, K. Masuda, H Kawamoto, H Koseki, and M Taniguchi
  • Journal Title: Blood Volume: 115 Pages: 230-237
  • Peer Reviewed
• [Journal Article] Thymic cysts originate from Foxn1 positive thymic medullary epithelium (2010)
  • Author(s): Vroegindeweij, E., S Crobach, M Itoic, R Satoh, S Zuklys, C Happee, W TV Germeraad, J J Cornelissen, T Cupedo, G A Hollander, H Kawamoto, and W van Ewijk
  • Journal Title: Mol Immunol Volume: 47 Pages: 1106-113
  • Peer Reviewed
• [Journal Article] An essential developmental checkpoint for production of the T cell lineage. (2010)
  • Author(s): Ikawa, T, S Hirose, K Masuda, K Kakugawa, R Satoh, A Shibano-Satoh, R Kominami, Y Katsura, H Kawamoto.
  • Journal Title: Science Volume: 329 Pages: 93-96
  • NAID: 40018275930
  • Peer Reviewed
• [Journal Article] Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19). (2010)
  • Author(s): Hirose K, T Inukai, J Kikuchi, Y Furukawa, T Ikawa, H Kawamoto, S H Oram, B Gottgens, N Kiyokawa, Y Miyagawa, H Okita, K Akahane, X Zhang, I Kuroda, H Honna, K Kagami, K Goi, Hu Kurosawa, A T Look, H Matsui, T Inaba, Kanji Sugita.
  • 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, Y Jin, H Ichikawa, T Ikawa, S Yamazaki, H Kawamoto, H Nakauchi, A Iwama
  • Journal Title: Cell Stem Cell Volume: 5 Pages: 279-286
  • Peer Reviewed
• [Journal Article] Innate production of Th2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphocytes. (2010)
  • Author(s): K.Moro, T.Yamada, M.Tanabe, T.Takeuchi, T.Ikawa, H.Kawamoto, J-I.Furusawa, M.Ohtani, H.Fujii, S.Koyasu
  • Journal Title: Nature Volume: 463 Pages: 540-544
  • Peer Reviewed
• [Journal Article] Thymic cysts originate from Foxn1 positive thymic medullary epithelium (2010)
  • Author(s): Vroegindeweij, E., S Crobach, M Itoic, R Satoh, S Zuklys, C Happee, W TV Germeraad, J J Cornelissen, T Cupedo, G A Hollander, H Kawamoto, W van Ewijk
  • Journal Title: Mol Immunol 47 Pages: 1106-113
  • Peer Reviewed
• [Journal Article] Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Vα14-Jα18 TCRα gene (2010)
  • Author(s): Watarai H, A Rybouchkin, N Hongo, Y Nagata, S Sakata, E Sekine, N Dashtsoodol, T Tashiro, S-I Fujii, K Shimizu, K Mori, K.Masuda, H Kawamoto, H Koseki, M Taniguchi
  • Journal Title: Blood 115 Pages: 230-237
  • Peer Reviewed
• [Journal Article] In vitro human G-CSF mobilized CD34+ derived T-cell progenitors fully mature in vivo (2010)
  • Author(s): Meek B, S Cloosen, C Borsotti, J Van Elssen, J Vanderlocht, M Schnijderberg, M van der Poel, B Leewis, R Hesselink, M G Manz, Y Katsura, H Kawamoto, W TV Germeraad, G MJ Bos
  • Journal Title: Blood 115 Pages: 261-264
  • Peer Reviewed
• [Journal Article] Innate production of Th2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphocytes (2010)
  • Author(s): Moro K., T.Yamada, M.Tanabe, T.Takeuchi, T.Ikawa, H.Kawamoto, J-I.Furusawa, M.Ohtani, H.Fujii, S.Koyasu
  • Journal Title: Nature 463 Pages: 540-544
  • Peer Reviewed
• [Journal Article] Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses (2009)
  • Author(s): Imada M, Masuda K, Satoh R, Ito Y, Goto Y, Matsuoka T, Endo S, Nakamura A, Kawamoto H, Takai T
  • Journal Title: Int. Immnol Volume: 1 Pages: 1151-1156
  • NAID: 10027389800
  • Peer Reviewed
• [Journal Article] A novel gene essential for the development of single positive thymocytes (2009)
  • Author(s): Kakugawa K., T. Yasuda, I. Miura, A. Kobayashi, H. Fukiage, R. Satoh, M. Matsuda, H. Koseki, S. Wakana, H. Kawamoto, H. Yoshida
  • Journal Title: Mol. Cell. Biol. Volume: 29 Pages: 5128-5135
  • Peer Reviewed
• [Journal Article] Direct hematological toxicity and illegitimate chromosomal recombination caused by the systemic activation of CreERT2 (2009)
  • Author(s): Higashi, A. Y., T. Ikawa, M. Muramatsu, A. N. Economides, A. Niwa, T. Okuda, A. J. Murphy, J. Rojas, T. Heike, T. Nakahata, H. Kawamoto, T. Kita, and Motoko Yanagita
  • Journal Title: J. Immunol Volume: 82 Pages: 5633-5640
  • Peer Reviewed
• [Journal Article] Notch activation in thymic epithelial cells induces development of thymic microenvironments (2009)
  • Author(s): K. Masuda, W. T. V. Germeraad, R. Satoh, M. Itoi, T. Ikawa, N. Minato, Y. Katsura, W. van Ewijk, and H. Kawamoto
  • Journal Title: Mol. Immunol. Volume: 46 Pages: 1756-1767
  • Peer Reviewed
• [Journal Article] Direct hematological toxicity and illegitimate chromosomal recom bination caused by the systemic activation of CreERT2 (2009)
  • Author(s): Higashi, A.Y., T.Ikawa, M.Muramatsu, A.N.Economides, A.Niwa, T.Okuda, A.J.Murphy, J.Rojas, T.Heike, T.Nakahata, H.Kawamoto, T.Kita, Motoko Yanagita
  • Journal Title: J.Immunol. 182 Pages: 5633-5640
  • Peer Reviewed
• [Journal Article] A novel gene essential for the development of single positive thymocytes (2009)
  • Author(s): Kakugawa K., T.Yasuda, I.Miura, A.Kobayashi, H.Fukiage, R.Satoh, M.Matsuda, H.Koseki, S.Wakana, H.Kawamoto, H.Yoshida
  • Journal Title: Mol.Cell.Biol 29 Pages: 5128-5135
  • Peer Reviewed
• [Journal Article] Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses (2009)
  • Author(s): Imada M, Masuda K, Satoh R, Ito Y, Goto Y, Matsuoka T, Endo S, Nakamura A, Kawamoto H, Takai T
  • Journal Title: Int.Immnol 21 Pages: 1151-1156
  • NAID: 10027389800
  • Peer Reviewed
• [Presentation] 造血幹細胞からT前駆細胞に至る系列決定の過程-古典的なミエロイド系/リンパ系二分法の概念からの脱却- (2012)
  • Author(s): 河本宏
  • Organizer: 第34回日本造血細胞移植学会総会
  • Place of Presentation: 大阪国際会議場(大阪市)(招待講演)
  • Year and Date: 2012-02-24
• [Presentation] Molecular mechanisms for the production and maintenance of the T cell lineage (2011)
  • Author(s): 河本宏
  • Organizer: 第40回日本免疫学会シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] Molecular mechanisms for the production and maintenance of the T cell lineage (2011)
  • Author(s): 河本宏
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 2011-11-28
• [Presentation] An essential developmental checkpoint for production of the T cell lineage. (2010)
  • Author(s): Tomokatsu Ikawa, Kawamoto Hiroshi, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-24
• [Presentation] Lineage restriction pathway in hematopoiesis : Revision of the classical concept of myeloid-lymphoid dichotomy (2010)
  • Author(s): 河本宏
  • Organizer: Immunology Seminar Series
  • Place of Presentation: ハーバード大学医学部(Boston, USA)
  • Year and Date: 2010-02-24
• [Presentation] 血液細胞の新しい分化経路モデル-混合型白血病細胞の起源についての考察- (2009)
  • Author(s): 河本宏
  • Organizer: 近畿血液学地方会
  • Place of Presentation: メルパルク京都(京都)
  • Year and Date: 2009-12-12
• [Presentation] T cell lineage determination : termination of myeloid potential in T cell progenitors (2009)
  • Author(s): 河本宏
  • Organizer: 第39回日本免疫学会シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] T cell lineage determination : termination of myeloid potential in T cell progenitors (2009)
  • Author(s): 河本宏
  • Organizer: 日本免疫学会シンポジウム
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02
• [Presentation] 血液細胞の新しい分化経路モデル-混合型白血病細胞の起源についての考察- (2009)
  • Author(s): 河本宏
  • Organizer: 小児血液学会
  • Place of Presentation: 東京ベイホテル東急(浦安)
  • Year and Date: 2009-11-27
• [Presentation] 血液細胞の新しい分化経路モデル-多様な細胞種は、どういう順序でつくられるか- (2009)
  • Author(s): 河本宏
  • Organizer: 数理生物学会
  • Place of Presentation: 東大駒場数理センター(東京)
  • Year and Date: 2009-09-09
• [Presentation] Induction of self-renewal program in developing hematopoietic progenitors by inhibiting their differentiation (2009)
  • Author(s): 河本宏
  • Organizer: JST-CIRM workshop
  • Place of Presentation: 京都フジタホテル(京都)
  • Year and Date: 2009-09-01
• [Presentation] リンパ球の起源と分化 (2009)
  • Author(s): 河本宏
  • Organizer: 比較免疫学会シンポジウム
  • Place of Presentation: 日本大学(藤沢)
  • Year and Date: 2009-08-05
• [Presentation] リンパ球から人工万能細胞(iPS細胞)をつくる (2009)
  • Author(s): 河本宏
  • Organizer: 動物細胞工学会大会
  • Place of Presentation: 筑波大学(つくば)
  • Year and Date: 2009-07-24
• [Presentation] Retention and termination of myeloid potential in T cell progenitors (2009)
  • Author(s): 河本宏
  • Organizer: Kyoto T cell Conference
  • Place of Presentation: 京大会館(京都)
  • Year and Date: 2009-06-02
• [Book] もっとよくわかる!免疫学 (2011)
  • Author(s): 河本宏
  • Total Pages: 221
  • Publisher: 羊土社
• [Book] もっとよくわかる!免疫学(実験医学別冊) (2011)
  • Author(s): 河本宏
  • Total Pages: 221
  • Publisher: 羊土社
• [Remarks] 成果/活動状況をHPで精力的に発表HP
  • URL: http://www.riken.go.jp/rcai.lymdev/home.html