The study of progenitor dedifferentiation in mouse testis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03168
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: National Institute for Basic Biology (2021-2023); Institute of Physical and Chemical Research (2020)
• Principal Investigator: Suzuki Shinnosuke 基礎生物学研究所, 生殖細胞研究部門, 助教 (00755994)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 精子幹細胞 / 精巣 / 不均一性

Outline of Final Research Achievements

In the mouse testis, clones of undifferentiated spermatogonia can interconvert between　spermatogonial stem cells (SSCs)　and progenitors, but the mechanism behind this process remains poorly understood. In this study, we aimed to understand the mechanism of interconversion between　SSCs　and progenitors by using single-cell RNA-seq analysis, analyzing reporter mice which can monitor this process, and developing an experimental system to efficiently analyze this process in vitro. As the results from RNA velocity analysis, we found a possibility that cells, which annotated the intermediate state between SSCs and progenitors could interconvert between SSCs and progenitors. Finally, our results strongly suggest that the inhibition of mTORC1 is involved in the interconversion between SSCs and progenitors.

Free Research Field

繁殖生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、マウス未分化精原細胞に含まれる亜集団を再定義し、亜集団内で可逆的な転換が生じている可能性を示すことができた。また、その可逆的な転換にmTORC1シグナルの抑制が関与している可能性も見出すことができた。ヒトにおいても少数のProgenitorがSSCsへと脱分化していることが1細胞レベルの遺伝子発現解析から予測されているため（Guo J et al., 2018, Cell Res）、mTORC1の抑制を活用することで、男性不妊を改善する治療法の確立に繋がることを期待する。