In situ genome sequencing resolves DNA sequence and structure in intact biological samples
Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/133498 |
| _version_ | 1826205337188827136 |
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| author | Payne, Andrew C Chiang, Zachary D Reginato, Paul L Mangiameli, Sarah M Murray, Evan M Yao, Chun-Chen Markoulaki, Styliani Earl, Andrew S Labade, Ajay S Jaenisch, Rudolf Church, George M Boyden, Edward S Buenrostro, Jason D Chen, Fei |
| author_facet | Payne, Andrew C Chiang, Zachary D Reginato, Paul L Mangiameli, Sarah M Murray, Evan M Yao, Chun-Chen Markoulaki, Styliani Earl, Andrew S Labade, Ajay S Jaenisch, Rudolf Church, George M Boyden, Edward S Buenrostro, Jason D Chen, Fei |
| author_sort | Payne, Andrew C |
| collection | MIT |
| description | Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously sequencing and imaging genomes within intact biological samples. We applied IGS to human fibroblasts and early mouse embryos, spatially localizing thousands of genomic loci in individual nuclei. Using these data, we characterized parent-specific changes in genome structure across embryonic stages, revealed single-cell chromatin domains in zygotes, and uncovered epigenetic memory of global chromosome positioning within individual embryos. These results demonstrate how IGS can directly connect sequence and structure across length scales from single base pairs to whole organisms. |
| first_indexed | 2024-09-23T13:11:24Z |
| format | Article |
| id | mit-1721.1/133498 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:11:24Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1334982021-10-28T03:55:36Z In situ genome sequencing resolves DNA sequence and structure in intact biological samples Payne, Andrew C Chiang, Zachary D Reginato, Paul L Mangiameli, Sarah M Murray, Evan M Yao, Chun-Chen Markoulaki, Styliani Earl, Andrew S Labade, Ajay S Jaenisch, Rudolf Church, George M Boyden, Edward S Buenrostro, Jason D Chen, Fei Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously sequencing and imaging genomes within intact biological samples. We applied IGS to human fibroblasts and early mouse embryos, spatially localizing thousands of genomic loci in individual nuclei. Using these data, we characterized parent-specific changes in genome structure across embryonic stages, revealed single-cell chromatin domains in zygotes, and uncovered epigenetic memory of global chromosome positioning within individual embryos. These results demonstrate how IGS can directly connect sequence and structure across length scales from single base pairs to whole organisms. 2021-10-27T19:53:10Z 2021-10-27T19:53:10Z 2021 2021-08-27T12:54:18Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133498 en 10.1126/SCIENCE.AAY3446 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Payne, Andrew C Chiang, Zachary D Reginato, Paul L Mangiameli, Sarah M Murray, Evan M Yao, Chun-Chen Markoulaki, Styliani Earl, Andrew S Labade, Ajay S Jaenisch, Rudolf Church, George M Boyden, Edward S Buenrostro, Jason D Chen, Fei In situ genome sequencing resolves DNA sequence and structure in intact biological samples |
| title | In situ genome sequencing resolves DNA sequence and structure in intact biological samples |
| title_full | In situ genome sequencing resolves DNA sequence and structure in intact biological samples |
| title_fullStr | In situ genome sequencing resolves DNA sequence and structure in intact biological samples |
| title_full_unstemmed | In situ genome sequencing resolves DNA sequence and structure in intact biological samples |
| title_short | In situ genome sequencing resolves DNA sequence and structure in intact biological samples |
| title_sort | in situ genome sequencing resolves dna sequence and structure in intact biological samples |
| url | https://hdl.handle.net/1721.1/133498 |
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