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

• Project/Area Number: 26461445
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka 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: ¥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.

Research Products

• [Presentation] SATB1 expression helps in identification of the lymphoid-lineage-biased trajectory of functionally fluctuating hematopoietic stem cells (2016)
  • 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
  • Int'l Joint Research
• [Presentation] SATB1 expression marks lymphoid-lineage-biased hematopoietic stem cells in mouse bone marrow (2016)
  • 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)
• [Presentation] SATB1 expression marks lymphoid-lineage-biased hematopoietic stem cells in mouse bone marrow (2016)
  • 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)
• [Presentation] SATB1 Expression Marks Lymphoid-Lineage-Biased Hematopoietic Stem Cells in Mouse Bone Marrow (2015)
  • 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
  • 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