細胞一つ一つの個性が手にとるように分かる新技術の開発に成功~疾患メカニズム解明から胚発生研究まで多様な応用に期待~

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2025-12-15 三重大学

三重大学と理化学研究所などの共同研究グループは、1細胞内のゲノムDNAとRNAを同時に高解像度解析できる新規1細胞解析技術「scRepli-RamDA-seq(scRR-seq)」を開発した。本手法は、DNAコピー数解析法scRepli-seqと高感度RNA解析法RamDA-seqを融合したもので、細胞ごとの遺伝情報と遺伝子発現を直接対応づけて解析できる点が特徴である。これにより、細胞周期進行の新規マーカーを発見するとともに、DNAコピー数変化と遺伝子発現が必ずしも単純な相関関係にないことを明らかにした。本技術は、疾患メカニズム解明、がん研究、胚発生研究など幅広い生命科学分野への応用が期待される。

細胞一つ一つの個性が手にとるように分かる新技術の開発に成功~疾患メカニズム解明から胚発生研究まで多様な応用に期待~
図1. 1細胞解析技術:scRepli-seqとRamDA-seqの概要

<関連情報>

scRepli-RamDA-seq: S期における遺伝子発現動態の解析を可能にするマルチオミクス技術 scRepli-RamDA-seq: a multi-omics technology enabling the analysis of gene expression dynamics during S-phase

Rawin Poonperm,Taiki Yoneda,Taito Imada,Saori Takahashi,Takako Ichinose,Hisashi Miura,Tetsutaro Hayashi,Mariko Kuse,Mika Yoshimura,Koji Nagao,Chikashi Obuse,Itoshi Nikaido,Ichiro Hiratani & Shin-ichiro Takebayashi
Nature Communications  Published:15 December 2025
DOI:https://doi.org/10.1038/s41467-025-64688-1

Abstract

Single-cell sequencing has advanced our understanding of cell-type diversity and heterogeneity. However, existing single-cell multi-omics methods lack the ability to monitor gene expression dynamics during S-phase progression. Here, we introduce single-cell (sc)Repli-RamDA-seq (scRR-seq), a multi-omics method that enables high-resolution DNA replication profiling and full-length total RNA sequencing from the same single cell in a haplotype-specific manner. scRR-seq generates DNA replication and RNA sequencing data comparable to individually obtained scRepli-seq and scRamDA-seq data, respectively. Unlike other scDNA/RNA-seq methods, scRR-seq allows one to tell the S-phase stage of a given cell based on the percentage of the replicated genome derived from scRepli-seq data. This facilitates analysis of gene expression dynamics during S-phase progression, enabling the identification of S-phase progression markers. scRR-seq also detects copy-number variation in non-S-phase cells and outperforms other scDNA/RNA-seq methods in various measures. Taken together, scRR-seq is a robust single-cell multi-omics method with promising potential for comprehensive genome/transcriptome analysis.

細胞遺伝子工学
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