In situ genome sequencing resolves DNA sequence and structure in intact biological samples
Name
nihms-1673034.pdf
Description
Accepted version
Size
2.94 MB
Format
Unknown
Checksum (MD5)
0135ee923c1b051a889e93d4b4b8a4bd
Author(s)
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
Date Issued
December 2020
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Version
Author's final manuscript
Abstract
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.
MIT Department
Program in Media Arts and Sciences (Massachusetts Institute of Technology)
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
McGovern Institute for Brain Research at MIT
Koch Institute for Integrative Cancer Research at MIT
Howard Hughes Medical Institute
Massachusetts Institute of Technology. Center for Neurobiological Engineering
Massachusetts Institute of Technology. Center for Extreme Bionics
Terms of Use
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.
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAY3446
