Identification of mesenchymal stem cell, which gives rise to hematopoiesis supporting cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Shimane University
• Principal Investigator: Miyagi Satoru 島根大学, 学術研究院医学・看護学系, 准教授 (20400997)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 間葉系幹細胞 / FZD5 / 造血支持細胞

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.

Free Research Field

幹細胞生物学

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。