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Elucidation of molecular mechanism of the robustness between T and B cell lineage

Research Project

Project/Area Number 16K09870
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKyoto University

Principal Investigator

Masuda Kyoko  京都大学, ウイルス・再生医科学研究所, 助教 (40565777)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords系列決定 / 系列頑健性 / ポリコーム遺伝子 / T細胞分化 / ミエロイド細胞 / T前駆細胞 / ポリコーム / Pax5 / B前駆細胞 / 血液免疫学 / T細胞 / B細胞
Outline of Final Research Achievements

It has been known that transcription factors play important roles for the determination of cell fate in the process of hematopoiesis. In this study, we tried to figure out how epigenetic mechanism regulate the lineage maintenance and the robustness. The analysis of mice conditionally deleted for polycomb genes in T cell progenitors revealed that T cell development was arrested at DN stage and those cells were converted to B cell lineage. Further, we examined whether non-T lineage cells also were able to be converted to another lineage. When progenitor cells of various lineage from mice conditionally deleted for polycomb gene in hematopoietic cells were cultured in the presence of cytokine cocktail, erythroid, megakaryocyte, B cell and T cell linage progenitors were converted to myeloid lineage. These results indicate that progenitors of all hematopoietic lineages retain latent myeloid potential beyond the lineage decision and their myeloid program is suppressed by polycomb genes.

Academic Significance and Societal Importance of the Research Achievements

細胞の運命決定に転写因子が深く関与することはすでに知られていたが、本研究により、転写因子だけではなくエピジェネティック制御によっても系列決定状態が規定されていることが示された。また全ての血球細胞は、系列が決定されたあとも潜在的にミエロイド細胞への分化能を有していることも示された。これらの結果は、血液細胞が進化の過程において、どのようなプロセスを経て各系列の細胞種を創出してきたか、各系列間での関係性はどのようなものであるかを考える上で非常に重要な知見であり、本研究が血液学をより深く理解するためにもたらした意義は非常に大きいものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (1 results) (of which Int'l Joint Research: 1 results) Book (7 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia.2017

    • Author(s)
      Seki M, Kimura S, Isobe T, Yoshida K, (13 authors), Masuda K, Kawamoto H, Ohki K, Kato M, Arakawa Y, Koh K, Hanada R, Moritake H, Akiyama M, Kobayashi R, Deguchi T, Hashii Y, Imamura T, Sato A, Kiyokawa N, Oka A, Hayashi Y, Takagi M, Manabe A, Ohara A, Horibe K, Sanada M, Iwama A, Mano H, Miyano S, Ogawa S, Takita J
    • Journal Title

      Nature Genetics

      Volume: 49 Issue: 8 Pages: 1274-1281

    • DOI

      10.1038/ng.3900

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs.2017

    • Author(s)
      Ichise H, Nagano S, Maeda T, Miyazaki M, Miyazaki Y, Kojima H, Yawata N, Yawata M, Tanaka H, Saji H, Masuda K, Kawamoto H
    • Journal Title

      Stem Cell Reports

      Volume: 9 Issue: 3 Pages: 853-867

    • DOI

      10.1016/j.stemcr.2017.07.020

    • NAID

      120006343758

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regeneration of tumor antigen-specific CTLs utilizing iPS technology2016

    • Author(s)
      Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M, Suzuki H, Yoshiato T, Yoshida K, Sanada M. Itonaga H, Imaizumi Y, Totoki Y, Munakata W, Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Masuda K, et al.
    • Journal Title

      Rinsho Ketsueki

      Volume: 57 Issue: 8 Pages: 1066-1073

    • DOI

      10.11406/rinketsu.57.1066

    • NAID

      130006882237

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Temporal and spatial requirements for Hoxa3 in mouse embryonic development2016

    • Author(s)
      Chojnowski JL, Trau HA, Masuda K, Manley N
    • Journal Title

      Developmental Biology

      Volume: 415 Issue: 1 Pages: 33-45

    • DOI

      10.1016/j.ydbio.2016.05.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney2016

    • Author(s)
      Sato Y, Mii A, Hamazaki Y, Fujita H, Nakata H, Masuda K, Nishiyama S, Shibuya S, Haga H, Ogawa O, Shimizu A, Narumiya S, Kaisho T, Arita M, Yanagisawa M, Miyasaka M, Sharma K, Minato N, Kawamoto H, and Yanagita M.
    • Journal Title

      JCI. Insight.

      Volume: 1 Issue: 11

    • DOI

      10.1172/jci.insight.87680

    • NAID

      120005820865

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regeneration of CD8αβ T cells from T cell-derived iPSC imparts potent tumor antigen-specific cytotoxicity.2016

    • Author(s)
      Maeda T, Nagano S, Ichise H, Kataoka K, Yamada D, Ogawa S, Koseki H, Kitawaki T, Kadowaki N, Takaori-Kondo A, Masuda K, Kawamoto H
    • Journal Title

      Cancer Research

      Volume: 76 Issue: 23 Pages: 6839-6850

    • DOI

      10.1158/0008-5472.can-16-1149

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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. Dev.

      Volume: 30 Issue: 22 Pages: 2475-2485

    • DOI

      10.1101/gad.290593.116

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] The effective role of HLA-C against NK cell-mediated rejection of HLA haplotype homozygous hematopoietic cells by haploidentical recipient.2016

    • Author(s)
      Hiroshi Ichise, Kyoko Masuda, Hiroshi Kawamoto
    • Organizer
      ThymUS
    • Place of Presentation
      ハワイ アメリカ合衆国
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] フローサイトメトリーQ&A2017

    • Author(s)
      増田喬子
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2017 Research-status Report
  • [Book] 週刊医学のあゆみ2016

    • Author(s)
      増田喬子,河本宏
    • Total Pages
      7
    • Publisher
      医師薬出版株式会社
    • Related Report
      2016 Research-status Report
  • [Book] 月間糖尿病2016

    • Author(s)
      河本宏,増田喬子
    • Total Pages
      8
    • Publisher
      医学出版
    • Related Report
      2016 Research-status Report
  • [Book] がん免疫療法ー腫瘍免疫学の最新知見から治療法のアップデートまでー2016

    • Author(s)
      河本宏,増田喬子,前田卓也
    • Total Pages
      5
    • Publisher
      羊土社
    • Related Report
      2016 Research-status Report
  • [Book] iPS細胞の安全・高品質な作製技術2016

    • Author(s)
      河本宏,増田喬子,前田卓也
    • Total Pages
      14
    • Publisher
      技術情報協会
    • Related Report
      2016 Research-status Report
  • [Book] 白血病学(下) ―最新の基礎,臨床研究―2016

    • Author(s)
      前田卓也、増田喬子,河本宏
    • Total Pages
      6
    • Publisher
      日本臨床社
    • Related Report
      2016 Research-status Report
  • [Book] 白血病学(下) ―最新の基礎,臨床研究―2016

    • Author(s)
      河本宏,増田喬子
    • Total Pages
      8
    • Publisher
      日本臨床社
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 抗原特異的制御性T細胞の作製法2016

    • Inventor(s)
      河本宏、坂口志文、増田喬子、廣田圭司、上堀淳二
    • Industrial Property Rights Holder
      河本宏、坂口志文、増田喬子、廣田圭司、上堀淳二
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-12-27
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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