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Variable SATB1 levels regulate hematopoietic stem cell heterogeneity with distinct lineage fate

Research Project

Project/Area Number 26461445
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

DOI Yukiko  大阪大学, 医学部附属病院, 医員 (60722288)

Co-Investigator(Kenkyū-buntansha) 金倉 譲  大阪大学, 医学系研究科, 教授 (20177489)
横田 貴史  大阪大学, 医学系研究科, 助教 (60403200)
織谷 健司  大阪大学, 医学系研究科, 准教授 (70324762)
Co-Investigator(Renkei-kenkyūsha) TAKEDA Junji  大阪大学, 大学院医学系研究科, 教授 (50163407)
Research Collaborator Kohwi-Shigematsu Terumi  University of California San Francisco, Department of Orofacial Sciences
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords造血幹細胞 / リンパ球初期分化 / SATB1 / 細胞分化
Outline of Final Research Achievements

Hematopoietic stem cells (HSCs) comprise a heterogeneous population. However, the mechanisms involved in maintaining this heterogeneity remain unclear. Here, we show that SATB1, a genome organizer, is involved in regulating the heterogeneity of HSCs. In conditional SATB1-knockout mice, SATB1 was indispensable for self-renewal and lymphopoiesis of adult HSCs. HSCs from SATB1/Tomato-knock-in reporter mice were classified based on SATB1/Tomato intensity. Transplantation, transcriptional and cell culture studies revealed stronger differentiation towards the lymphocytic lineage with high SATB1 levels, whereas SATB1- HSCs followed the myeloid lineage. Importantly, the SATB1- and SATB1+ HSC population were interconvertible upon transplantation. These results suggest that SATB1 levels regulate the maintenance of HSC multipotency, variations in which contribute to HSC heterogeneity.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2016 2015 2014

All Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] SATB1 expression helps in identification of the lymphoid-lineage-biased trajectory of functionally fluctuating hematopoietic stem cells2016

    • Author(s)
      Yukiko Doi
    • Organizer
      The 58th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      San Diego Convention Center, San Diego, CA, USA
    • Related Report
      2016 Annual Research 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
    • Organizer
      第78回日本血液学会学術集会 一般口演60 血球分化
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] SATB1 expression marks lymphoid-lineage-biased hematopoietic stem cells in mouse bone marrow2016

    • Author(s)
      Yukiko Doi
    • Organizer
      第78回日本血液学会学術集会 SETP4 Hematopoietic stem cell
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] SATB1 Expression Marks Lymphoid-Lineage-Biased Hematopoietic Stem Cells in Mouse Bone Marrow2015

    • Author(s)
      Yukiko Doi, Takafumi Yokota, Tomohiko Ishibashi, Yusuke Satoh, Michiko Ichii, Akira Tanimura, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
    • Organizer
      57th ASH annual meeting & Exposition
    • Place of Presentation
      Orange County Convention Center, Orlando, Florida, U. S. A.
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] リンパ球造血におけるクロマチン構造制御蛋白の機能解析2014

    • Author(s)
      土居由貴子, 横田貴史, 谷村朗, 齋藤則充, 一井倫子, 江副幸子, 柴山浩彦, 織谷健司, 金倉譲
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Year and Date
      2014-11-01
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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