Analysis of epigenome infertiity mechanism by the state-of-art single cell and ultrtrace histone modification methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 19KK0183
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Yokohama City University
• Principal Investigator: OHBO Kazuyuki 横浜市立大学, 医学研究科, 教授 (70250751)
• Co-Investigator(Kenkyū-buntansha): 富澤 信一 横浜市立大学, 医学部, 講師 (00704628) ; 鈴木 絢子 東京大学, 大学院新領域創成科学研究科, 准教授 (00770348)
• Project Period (FY): 2019-10-07 – 2024-03-31
• Keywords: 幹細胞 / エピジェネティクス / 精子形成

Outline of Final Research Achievements

Spermatogonial stem cells adopt a mitotic mode in which intercellular bridges are present due to incomplete cytokinesis. Therefore, only one spermatogonia is a stem cell and two or more connected spermatogonia are considered progenitors that have lost their stem cell activity. On the other hand, advances in genome-wide gene expression analysis and marker studies have begun to reveal the heterogeneity of undifferentiated spermatogonia. In this study, the scNMT method, the latest comprehensive single-cell analysis, was adopted from overseas and applied to elucidate the actual situation of undifferentiated spermatogonia. The existence of a group of H3K4 methyltransferases has also been reported. The functional analysis of these molecules in undifferentiated spermatogonia was carried out in collaboration with an overseas group that had extensively genetically modified these molecules.

Free Research Field

発生学

Academic Significance and Societal Importance of the Research Achievements

日本の研究領域は、欧米中国との格差が広がっている。特に次世代シークエンサーの出現後、ゲノムワイドにヒストンやDNA修飾、遺伝子発現の情報が入手可能となり、エピゲノム研究が急速に進歩を遂げた。さらに少ない材料からのエピゲノム解析も急速な進歩を見せている。しかし、日本は、この流れに遅れを取っていることは否めない。そこで、最先端のシングルセルマルチオミックス研究と、ES細胞を材料にH3K4me3修飾を中心に精力的な研究を行っている高い研究レベルをもつグループとの国際共同研究を行い、その成果を私どもが長年行っている精子幹細胞研究に反映させ、より高いレベルの研究へと結びつけた。