Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2025-01-22 DOI:10.1038/s41467-025-56331-w
Dongsheng Mao, Xiaochen Tang, Runchi Zhang, Song Hu, Hongquan Gou, Penghui Zhang, Wenxing Li, Qiuhui Pan, Bing Shen, Xiaoli Zhu
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Abstract

Understanding the heterogeneity of epigenetic modifications within single cells is pivotal for unraveling the nature of the complexity of gene expression and cellular function. In this study, we have developed a strategy based on multichrome encoding and “AND” Boolean logic recognition for multiplexed, spatially resolved imaging of single-cell RNA epigenetic modifications, termed as PRoximity Exchange-assisted Encoding of Multichrome (PREEM). Through the implementation of this strategy, we can now map the expression and nuclear distribution of multiple site-specific RNA N6-methyladenosine (m6A) modifications at the single-molecule resolution level in single-cells, and reveal the previously unknown heterogeneity. Notably, we demonstrate how these patterns change after treatment with various drugs. Moreover, cyclic imaging with tailed DNA self-assembly further suggest the scalability and adaptability of PREEM’s design. As an innovative epigenetic modification imaging tool, PREEM not only broadens the horizons of single-cell epigenetics research, enabling joint analysis of multiple targets beyond the limitations of imaging channels, but also reveals cell-to-cell variability, thereby enhancing our capacity to explore cellular functions.

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基于多色编码的多路复用,空间分辨成像揭示单细胞RNA表观遗传修饰异质性
了解单细胞内表观遗传修饰的异质性对于揭示基因表达和细胞功能复杂性的本质至关重要。在这项研究中,我们开发了一种基于多色编码和“与”布尔逻辑识别的策略,用于单细胞RNA表观遗传修饰的多路、空间分辨成像,称为近距离交换辅助多色编码(PREEM)。通过这一策略的实施,我们现在可以在单细胞的单分子分辨率水平上绘制多位点特异性RNA n6 -甲基腺苷(m6A)修饰的表达和核分布,并揭示以前未知的异质性。值得注意的是,我们展示了这些模式在使用各种药物治疗后是如何变化的。此外,带有尾部DNA自组装的循环成像进一步表明了PREEM设计的可扩展性和适应性。作为一种创新的表观遗传修饰成像工具,PREEM不仅拓宽了单细胞表观遗传学研究的视野,可以超越成像通道的限制对多个靶点进行联合分析,而且可以揭示细胞间的差异性,从而增强我们探索细胞功能的能力。
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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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