| Project/Area Number |
16K09819
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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 | Tohoku University |
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Principal Investigator |
Okitsu Yoko 東北大学, 医学系研究科, 助教 (80451558)
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| Project Period (FY) |
2016-01-27 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| Keywords | GATA-2 / 間葉系幹細胞 / 再生不良性貧血 / 造血微小環境 |
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| Outline of Final Research Achievements |
The bone marrow (BM) microenvironment comprises multiple stem cell niches derived from BM mesenchymal stem cells (BM-MSCs). Previous in vitro analyses have suggested that transcription factor GATA2 plays an important role in adipocyte differentiation of BM-mesenchymal stem cells as well as in hematopoietic support, but the role of GATA2 in vivo remains unknown. We evaluated GATA2 effects in BM-MSC in vivo. We did not find any phenotypic changes when Gata2 was deleted with BM-MSC-related gene promoters, such as Nestin, Prx1, and Lepr, except for a significant decrease in the colony number of Gata2f/f/Prx1-Cre mice. Noticeably, there was a significant decrease in the percentage of the CMP fraction when Gata2 was deleted in all BM cells except for hematopoietic cells, after normal BM cells were transplanted into irradiated Gata2f/f/ER-Cre mice, with Gata2 subsequently knocked out by tamoxifen administration. In conclusion, GATA2 could affect the function of BM-MSCs in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，in vivoにおけるGata2の骨髄微小環境での機能を検討してきた．Gata2は造血前駆細胞における増殖や分化の制御のみではなく，BM-MSCにおいてもニッチとしての機能を制御し，HSCから骨髄球系共通前駆細胞およびリンパ球系共通前駆細胞への分化調節を担っている可能性があり，この機序としてはITGA11やITGB3，カテプシンGをはじめとした細胞接着因子や走化性因子が候補として考えられた．しかし，BM-MSCからHSCへのシグナル伝達経路に関しては検討が不十分であり，今後の課題として取り組んでいくべき点であると思われた．
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