Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56331-w |
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| author | Dongsheng Mao Xiaochen Tang Runchi Zhang Song Hu Hongquan Gou Penghui Zhang Wenxing Li Qiuhui Pan Bing Shen Xiaoli Zhu |
| author_facet | Dongsheng Mao Xiaochen Tang Runchi Zhang Song Hu Hongquan Gou Penghui Zhang Wenxing Li Qiuhui Pan Bing Shen Xiaoli Zhu |
| author_sort | Dongsheng Mao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-22f3e6c3b1954653b36a92449e85f836 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-22f3e6c3b1954653b36a92449e85f8362025-01-26T12:41:17ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56331-wMultichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneityDongsheng Mao0Xiaochen Tang1Runchi Zhang2Song Hu3Hongquan Gou4Penghui Zhang5Wenxing Li6Qiuhui Pan7Bing Shen8Xiaoli Zhu9Shanghai Tenth People’s Hospital of Tongji UniversityDepartment of Clinical Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineShanghai Tenth People’s Hospital of Tongji UniversityShanghai Pudong New Area People’s HospitalShanghai Tenth People’s Hospital of Tongji UniversityShanghai Pudong New Area People’s HospitalShanghai Tenth People’s Hospital of Tongji UniversityDepartment of Clinical Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineShanghai Tenth People’s Hospital of Tongji UniversityShanghai Tenth People’s Hospital of Tongji UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56331-w |
| spellingShingle | Dongsheng Mao Xiaochen Tang Runchi Zhang Song Hu Hongquan Gou Penghui Zhang Wenxing Li Qiuhui Pan Bing Shen Xiaoli Zhu Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity Nature Communications |
| title | Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity |
| title_full | Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity |
| title_fullStr | Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity |
| title_full_unstemmed | Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity |
| title_short | Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity |
| title_sort | multichrome encoding based multiplexed spatially resolved imaging reveals single cell rna epigenetic modifications heterogeneity |
| url | https://doi.org/10.1038/s41467-025-56331-w |
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