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Identification of molecular mechanisms activating hematopoietic stem cells by monitoring expression levels of a new stem-cell marker ESAM

Research Project

Project/Area Number 15K09475
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Takafumi Yokota  大阪大学, 医学系研究科, 講師 (60403200)

Co-Investigator(Kenkyū-buntansha) 金倉 譲  大阪大学, 医学系研究科, 教授 (20177489)
織谷 健司  国際医療福祉大学, 医学部, 教授 (70324762)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords造血幹細胞 / 白血病幹細胞 / ヒト急性骨髄性白血病 / 幹細胞マーカー / 細胞のゆらぎ / ヒト造血幹細胞 / ヒト急性白血病 / 表面抗原
Outline of Final Research Achievements

We previously demonstrated that the endothelial-cell selective adhesion molecule (ESAM) is an important marker of HSCs in humans. In the present study, we have exploited ESAM expression levels as an index to analyze the molecular mechanisms regulating the status of hematopoietic stem cells, and have applied findings to develop new strategies for diagnosis and treatment of human acute leukemia. Our study has revealed that many of human acute myeloid leukemia cases highly expressed ESAM on their tumor cells. We also found that leukemia stem cells (LSCs) represent ESAM expression, of which levels are heterogeneous and are fluctuating at single cell levels according to the proliferating status of LSCs. The TGFβ signaling pathway is autonomously involved in inducing heterogeneity in ESAM expression in the LSC population. The fluctuation is thought to confer certain benefits to LSCs, such as drug resistance and promoting invasiveness.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (22 results)

All 2018 2017 2016 2015 Other

All Journal Article (8 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 7 results) Remarks (1 results)

  • [Journal Article] Identification of MS4A3 as a reliable marker for early myeloid differentiation in human hematopoiesis.2018

    • Author(s)
      Ishibashi T, Yokota T, Satoh Y, Ichii M, Sudo T, Doi Y, Ueda T, Nagate Y, Hamanaka Y, Tanimura A, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 3 Pages: 2338-2343

    • DOI

      10.1016/j.bbrc.2017.12.117

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] リンパ球造血に関する最近の知見2017

    • Author(s)
      横田貴史
    • Journal Title

      実験医学

      Volume: 35 Pages: 3063-3070

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 急性リンパ性白血病の遺伝子異常2017

    • Author(s)
      横田貴史、金倉譲
    • Journal Title

      血液内科

      Volume: 74 Pages: 103-108

    • NAID

      40021065731

    • Related Report
      2016 Research-status Report
  • [Journal Article] Endothelial cell-selective adhesion molecule expression in hematopoietic stem/progenitor cells is essential for erythropoiesis recovery after bone marrow injury.2016

    • Author(s)
      Sudo T, Yokota T, Okuzaki D, Ueda T, Ichii M, Ishibashi T, Isono T, Habuchi Y, Oritani K, Kanakura Y.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 4 Pages: e0154189-e0154189

    • DOI

      10.1371/journal.pone.0154189

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic abnormalities associated with acute lymphoblastic leukemia2016

    • Author(s)
      Yokota T, Kanakura Y
    • Journal Title

      Cancer Science

      Volume: in press Issue: 6 Pages: 721-725

    • DOI

      10.1111/cas.12927

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.2016

    • Author(s)
      Ishibashi T, Yokota T, Tanaka H, Ichii M, Sudo T, Satoh Y, Doi Y, Ueda T, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
    • Journal Title

      Experimental Hematology

      Volume: 44 Issue: 4 Pages: 269-281

    • DOI

      10.1016/j.exphem.2015.12.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of endothelial antigen ESAM in activated hematopoietic stem cells2015

    • Author(s)
      Sudo T, Yokota T, Kanakura Y
    • Journal Title

      Rinsho Ketsueki

      Volume: 56 Issue: 5 Pages: 464-474

    • DOI

      10.11406/rinketsu.56.464

    • NAID

      130005076019

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of osteoblast stimulating factor 5 as a negative regulator in the B-lymphopoietic niche.2015

    • Author(s)
      Fujita N, Ichii M, Maeda T, Saitoh N, Yokota T, Yamawaki K, Kakitani M, Tomizuka K, Oritani K, Kanakura Y
    • Journal Title

      Experimental Hematology

      Volume: 43 Issue: 11 Pages: 963-973

    • DOI

      10.1016/j.exphem.2015.07.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Endothelial Cell-Selective Adhesion Molecule (ESAM) plays important roles in the adult-type hemoglobin synthesis during fetal erythropoiesis2017

    • Author(s)
      Tomoaki Ueda, Takafumi Yokota, Yasuhiro Shingai, Yukiko Doi, Tomohiko Ishibashi, Takao Sudo, Akira Tanimura, Michiko Ichii, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, and Yuzuru Kanakura
    • Organizer
      The American Society of Hematology 59th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Variable Expression Levels of the Hematopoietic Stem Cell Surface Antigen ESAM Depict Heterogeneity and Fluctuations in Leukemic Stem Cells2017

    • Author(s)
      Yasuhiro Shingai, Takafumi Yokota, Tomoaki Ueda, Yukiko Doi, Tomohiko Ishibashi, Akira Tanimura, Michiko Ichii,Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
    • Organizer
      The American Society of Hematology 59th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SATB1 expression is useful to identify the lymphoid-lineage-biased trajectory of functionally fluctuatinghematopoietic stem cells.2017

    • Author(s)
      Yukiko Doi, Takafumi Yokota, Tomohiko Ishibashi, Yusuke Satoh, Michiko Ichii, Akira Tanimura, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Stressed microenvironment induced by 5-FU promotes the proliferation of HSPC in bone marrow2017

    • Author(s)
      Takao Sudo, Takafumi Yokota, Yuzuru Kanakura, Masaru Ishii
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 造血幹細胞表面抗原ESAMを用いた白血病幹細胞の不均一性とゆらぎの解析2017

    • Author(s)
      新開泰宏、横田貴史、上田智朗、土居由貴子、石橋智彦、谷村 朗、一井倫子、江副 幸子、柴山浩彦、織谷健司、金倉 譲
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Endothelial Cell-Selective Adhesion Molecule (ESAM) Is Required for the Ontogeny of Definitive Hematopoietic System in Mice2016

    • Author(s)
      Tomoaki Ueda, Takafumi Yokota, Yasuhiro Shingai, Yukiko Doi, Tomohiko Ishibashi, Takao Sudo, Yasuhiro Nagate, Akira Tanimura, Masahiro Tokunaga, Jiro Fujita, Michiko Ichii, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, and Yuzuru Kanakura
    • Organizer
      The American Society of Hematology 58th Annual Meeting
    • Place of Presentation
      San Diego (California, USA)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] SATB1 expression helps in identification of the lymphoid-lineage-biased trajectory of functionally fluctuating hematopoietic stem cells2016

    • Author(s)
      Yukiko Doi, Takafumi Yokota, Yusuke Satoh, Tomoaki Ueda, Yasuhiro Shingai, Michiko Ichii, Akira Tanimura, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Terumi Kohwi-Shigematsu, Yuzuru Kanakura
    • Organizer
      The American Society of Hematology 58th Annual Meeting
    • Place of Presentation
      San Diego (California, USA)
    • Year and Date
      2016-12-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] SATB1 expression marks lymphoid-lineage-biased hematopoietic stem cells in mouse bone marrow2016

    • Author(s)
      土居由貴子, 横田貴史, 石橋知彦, 佐藤友亮, 一井倫子, 谷村 朗, 江副幸子, 柴山浩彦, 織谷健司, 金倉譲
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Endothelial antigen ESAM is a human HSC marker associated with a subset of human leukemias2016

    • Author(s)
      石橋知彦, 横田貴史, 田中宏和, 一井倫子, 数藤孝雄, 佐藤友亮, 土居由貴子, 上田智明, 新開泰宏, 谷村 朗, 濱中有理, 江副幸子, 柴山浩彦, 織谷健司, 金倉譲
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] ESAM is required for the ontogeny of definitive hematopoietic system in mice2016

    • Author(s)
      上田智明, 横田貴史, 土居由貴子, 石橋知彦, 数藤孝雄, 谷村 朗, 徳永正浩, 一井倫子, 江副幸子, 柴山浩彦, 織谷健司, 金倉譲
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] SATB1 expression marks lymphoid-lineage-biased hematopoietic stem cells in mouse bone marrow.2015

    • Author(s)
      Doi Y, Yokota T, Ishibashi1 T, Satoh Y, Ichii M, Tanimura A, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
    • Organizer
      The American Society of Hematology 57th Annual Meeting
    • Place of Presentation
      The Orange County Convention Center, Orlando, FL, USA
    • Year and Date
      2015-12-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.2015

    • Author(s)
      Ishibashi T,Yokota T, Tanaka H, Ichii1 M, Sudo T, Satoh Y, Doi Y, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
    • Organizer
      The American Society of Hematology 57th Annual Meeting
    • Place of Presentation
      The Orange County Convention Center, Orlando, FL, USA
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Endothelial cell-selective adhesion molecule is a novel human hematopoietic stem cell marker associated with a subset of human leukemias2015

    • Author(s)
      Ishibashi T,Yokota T, Tanaka H, Ichii1 M, Sudo T, Satoh Y, Doi Y, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
    • Organizer
      The 44th Annual Scientific Meeting of International Society of Exoerimental Hematology (ISEH)
    • Place of Presentation
      Kyoto International Conference Center, Kyoto Japan
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Remarks] 大阪大学血液・腫瘍内科ホームページ

    • URL

      http://www.hematology.pro/index.html

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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