2025-10-10 清華大学
<関連情報>
- https://www.tsinghua.edu.cn/en/info/1245/14509.htm
- https://www.cell.com/cell/abstract/S0092-8674(25)01034-7
単一細胞の新生転写は、疎なゲノム利用と可塑性を明らかにする Single-cell nascent transcription reveals sparse genome usage and plasticity
Shaoqian Ma ∙ Yantao Hong ∙ Junhan Chen ∙ Jingzhao Xu ∙ Xiaohua Shen
Cell Published:September 26, 2025
DOI:https://doi.org/10.1016/j.cell.2025.09.003
Highlights
- <3.1% of the genome is transcribed per cell, showing limited genome engagement
- Single-cell transcription is stochastic, especially in intergenic heterochromatin
- mRNA and proximal/distal ncRNA exhibit distinct transcription kinetics and regulation
- mRNA/ncRNA transcription diversity signals cellular plasticity—preceding fate commitment
Summary
Understanding cell diversification from a common genome in metazoans requires single-cell transcriptional analysis. We introduce single-cell full-length EU-labeled nascent RNA sequencing (scFLUENT-seq), a single-cell nascent RNA sequencing method using brief 10-min metabolic labeling to capture genome-wide transcription. Surprisingly, individual cells—from splenic lymphocytes to pluripotent stem cells—transcribe only ∼0.02%–3.1% of the genome, versus >80% in bulk, revealing limited genome engagement and profound cell-type and cell-to-cell heterogeneity. Intergenic transcription, especially from heterochromatin, is pervasive and stochastic. Promoter-associated antisense and genic transcription rarely co-occur in the same cell. Proximal intergenic transcription involves both gene readthrough and independent initiation, while distal intergenic transcription is largely independent of neighboring genes and correlates with increased transcriptional diversity, a hallmark of cellular plasticity. Although global RNA synthesis and turnover are coupled in bulk, individual mRNA transcription and decay are poorly coordinated in single cells, suggesting noise-buffering mechanisms. Overall, scFLUENT-seq uncovers complex coding and noncoding transcriptional dynamics that underlie single-cell heterogeneity and state transitions.
