通过基于体内代谢 RNA 标记的 scRNA-seq,Dyna-vivo-seq 揭示急性肾损伤期间的细胞 RNA 动态变化

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2024-11-14 DOI:10.1038/s41467-024-54202-4
Kun Yin, Yiling Xu, Ye Guo, Zhong Zheng, Xinrui Lin, Meijuan Zhao, He Dong, Dianyi Liang, Zhi Zhu, Junhua Zheng, Shichao Lin, Jia Song, Chaoyong Yang
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摘要

基因组学的一个基本目标是追踪基因表达程序的变化。虽然基于代谢 RNA 标记的单细胞 RNA 测序能深入了解生物过程的时间性,但其仅适用于体外模型的局限性给体内基因表达动态研究带来了挑战。在本文中,我们介绍了Dyna-vivo-seq,这是一种通过检测新旧RNA在单细胞水平上实现体内时间分辨动态转录谱分析的策略。新 RNA 为揭示细胞异质性提供了一个额外的维度。利用新 RNA,我们在近端肾小管(PT)细胞中发现了两种不同的高代谢标记和低代谢标记群体。此外,我们还发现了 90 个在雌性小鼠急性肾损伤期间快速反应的转录因子,突显出高代谢标记的近端肾小管细胞对损伤表现出更高的易感性。Dyna-vivo-seq为活体单细胞水平的动态转录组表征提供了一个强大的工具,在生物医学应用方面前景广阔。
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Dyna-vivo-seq unveils cellular RNA dynamics during acute kidney injury via in vivo metabolic RNA labeling-based scRNA-seq

A fundamental objective of genomics is to track variations in gene expression program. While metabolic RNA labeling-based single-cell RNA sequencing offers insights into temporal biological processes, its limited applicability only to in vitro models challenges the study of in vivo gene expression dynamics. Herein, we introduce Dyna-vivo-seq, a strategy that enables time-resolved dynamic transcription profiling in vivo at the single-cell level by examining new and old RNAs. The new RNAs can offer an additional dimension to reveal cellular heterogeneity. Leveraging new RNAs, we discern two distinct high and low metabolic labeling populations among proximal tubular (PT) cells. Furthermore, we identify 90 rapidly responding transcription factors during the acute kidney injury in female mice, highlighting that high metabolic labeling PT cells exhibit heightened susceptibility to injury. Dyna-vivo-seq provides a powerful tool for the characterization of dynamic transcriptome at the single-cell level in living organism and holds great promise for biomedical applications.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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