| Project/Area Number |
26461445
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
DOI Yukiko 大阪大学, 医学部附属病院, 医員 (60722288)
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| 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)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKEDA Junji 大阪大学, 大学院医学系研究科, 教授 (50163407)
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| Research Collaborator |
Kohwi-Shigematsu Terumi University of California San Francisco, Department of Orofacial Sciences
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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)
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| Keywords | 造血幹細胞 / リンパ球初期分化 / SATB1 / 細胞分化 |
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| 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.
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