Identification of mesenchymal stem cell, which gives rise to hematopoiesis supporting cells
| Project/Area Number |
19K08865
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Shimane University |
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Principal Investigator |
Miyagi Satoru 島根大学, 学術研究院医学・看護学系, 准教授 (20400997)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 間葉系幹細胞 / FZD5 / 造血支持細胞 / 造血幹細胞 / ニッチ / 細胞系譜追跡 |
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| Outline of Research at the Start |
骨髄中の一部の間質細胞は血液細胞の産生を助ける働きを持つ（この間質細胞を造血支持細胞と呼ぶ。）これまでに、複数の造血支持細胞が同定されているが、これら造血支持細胞間の関係性や造血支持細胞がどのように生まれて来るのかは明らかになっていない。本研究では、造血支持細胞の元となると予想される間葉系幹細胞とその子孫細胞を別個に標識可能なマウスを用いて、間葉系幹細胞から造血支持細胞が産生される過程を明らかにする。
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| Outline of Final Research Achievements |
A previous study showed that the FZD5 expression distinguishes immature human mesenchymal stem cells (MSC) in vitro, and the FZD5 is crucial for maintaining the stemness of MSC. Therefore, we generated a transgenic mouse (Fzd5-CreERT-tFP635) that expresses CreERT and the TurboFP635 (tFP635) under the transcriptional control of the Fzd5 gene. In the bone marrow (BM) of the mice, tFP635 was preferentially expressed in MSC, Leptin receptor-expressing MSC (LepR+MSCs), and some Pdgfrα+ Sca1+ MSC (PαS). Inducible lineage tracing with the strain at the adult stage showed that Fzd5-expressing cells and their descendants were progressively dominant in LepR+MSC and PαS, and the cells persisted for one year. These results showed that our transgenic mouse marks two different types of MSC, LepR+MSC and PαS. We also found that tFP635-PDGFRa+Sca1+ stromal cells (tFP635-PDSP) are a putative novel MSC fraction.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、血液産生を助ける働きのある造血支持細胞が、どのようにして成体内で維持されるかを明らかにすることを目的とした。このため、独自にレポーターマウスを作成・解析を行い、作成したレポーターマウスが既知の造血支持細胞をマーキングすることを見出した。さらに、骨髄中に造血支持細胞を産生する能力を持つと予想される新規の細胞を同定した。この結果は、血液産生の制御機構や白血病などの血液のガンの発症機構の解明につながる知見である。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] The chromatin binding protein Phf6 restricts the self-renewal of hematopoietic stem cells.2019
Author(s)
Miyagi S, Sroczynska P, Kato Y, Nakajima-Takagi Y, Oshima M, Rizq O, Takayama N, Saraya A, Mizuno S, Sugiyama F, Takahashi S, Matsuzaki Y, Christensen J, Helin K, and Iwama A.
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Journal Title
Blood
Volume: -
Issue: 23
Pages: 2495-2506
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genome-Wide Mapping of Bivalent Histone Modifications in Hepatic Stem/Progenitor Cells2019
Author(s)
Kanayama K, Chiba T, Oshima Kanzaki H, Koide S, Saraya A, Miyagi S, Mimura N, Kusakabe Y, Saito T, Ogasawara S, Suzuki E, Ooka Yoshihiko, Maruyama H, Iwama A, Kato N.
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Journal Title
Stem Cells Int
Volume: 2019
Pages: 9789240-9789240
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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