Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics
Abstract Single-cell three-dimensional (3D) genome techniques have advanced our understanding of cell-type-specific chromatin structures in complex tissues, yet current methodologies are limited in cell throughput. Here we introduce a high-throughput single-cell Hi-C (dscHi-C) approach and its trans...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-025-00770-8 |
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| author | Honggui Wu Maoxu Wang Yinghui Zheng X. Sunney Xie |
| author_facet | Honggui Wu Maoxu Wang Yinghui Zheng X. Sunney Xie |
| author_sort | Honggui Wu |
| collection | DOAJ |
| description | Abstract Single-cell three-dimensional (3D) genome techniques have advanced our understanding of cell-type-specific chromatin structures in complex tissues, yet current methodologies are limited in cell throughput. Here we introduce a high-throughput single-cell Hi-C (dscHi-C) approach and its transcriptome co-assay (dscHi-C-multiome) using droplet microfluidics. Using dscHi-C, we investigate chromatin structural changes during mouse brain aging by profiling 32,777 single cells across three developmental stages (3 months, 12 months, and 23 months), yielding a median of 78,220 unique contacts. Our results show that genes with significant structural changes are enriched in pathways related to metabolic process and morphology change in neurons, and innate immune response in glial cells, highlighting the role of 3D genome organization in physiological brain aging. Furthermore, our multi-omics joint assay, dscHi-C-multiome, enables precise cell type identification in the adult mouse brain and uncovers the intricate relationship between genome architecture and gene expression. Collectively, we developed the sensitive, high-throughput dscHi-C and its multi-omics derivative, dscHi-C-multiome, demonstrating their potential for large-scale cell atlas studies in development and disease. |
| format | Article |
| id | doaj-art-b355ffe10a354d66ae6ea9b4949816b7 |
| institution | Kabale University |
| issn | 2056-5968 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj-art-b355ffe10a354d66ae6ea9b4949816b72025-01-26T12:15:03ZengNature Publishing GroupCell Discovery2056-59682025-01-0111111310.1038/s41421-025-00770-8Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomicsHonggui Wu0Maoxu Wang1Yinghui Zheng2X. Sunney Xie3Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking UniversityBiomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking UniversityBiomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking UniversityBiomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking UniversityAbstract Single-cell three-dimensional (3D) genome techniques have advanced our understanding of cell-type-specific chromatin structures in complex tissues, yet current methodologies are limited in cell throughput. Here we introduce a high-throughput single-cell Hi-C (dscHi-C) approach and its transcriptome co-assay (dscHi-C-multiome) using droplet microfluidics. Using dscHi-C, we investigate chromatin structural changes during mouse brain aging by profiling 32,777 single cells across three developmental stages (3 months, 12 months, and 23 months), yielding a median of 78,220 unique contacts. Our results show that genes with significant structural changes are enriched in pathways related to metabolic process and morphology change in neurons, and innate immune response in glial cells, highlighting the role of 3D genome organization in physiological brain aging. Furthermore, our multi-omics joint assay, dscHi-C-multiome, enables precise cell type identification in the adult mouse brain and uncovers the intricate relationship between genome architecture and gene expression. Collectively, we developed the sensitive, high-throughput dscHi-C and its multi-omics derivative, dscHi-C-multiome, demonstrating their potential for large-scale cell atlas studies in development and disease.https://doi.org/10.1038/s41421-025-00770-8 |
| spellingShingle | Honggui Wu Maoxu Wang Yinghui Zheng X. Sunney Xie Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics Cell Discovery |
| title | Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics |
| title_full | Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics |
| title_fullStr | Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics |
| title_full_unstemmed | Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics |
| title_short | Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics |
| title_sort | droplet based high throughput 3d genome structure mapping of single cells with simultaneous transcriptomics |
| url | https://doi.org/10.1038/s41421-025-00770-8 |
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