期刊
SCIENCE
卷 371, 期 6532, 页码 908-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aay3446
关键词
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资金
- Allen Institute Distinguished Investigator award
- NIH [R21HG009749, DP5OD024583, 1RM1HG008525, 1R01DA045549, 2R01DA029639, 1R01NS102727, UF1NS107697, 1U19MH114821, 1R01EB024261, 1R01MH110932, R37 CA084198, R01 MH104610-20, RM1HG008525, 1R01NS087950]
- Open Philanthropy Project
- HHMI
- HHMI-Simons Faculty Scholars Program
- IARPA [D16PC00008]
- U.S. Army Research Laboratory
- U.S. Army Research Office [W911NF1510548]
- U.S.-Israel Binational Science Foundation grant [2014509]
- NIH Director's Pioneer Award [1DP1NS087724]
- NSERC PGS-D awards
- NHGRI training grant [T32HG002295]
- Harvard Quantitative Biology Initiative
In situ genome sequencing (IGS) allows for sequencing and imaging of genomes within intact biological samples, providing spatial localization of genomic loci and revealing parent-specific changes in genome structure across embryonic stages, single-cell chromatin domains in zygotes, and epigenetic memory of global chromosome positioning within individual embryos. These results demonstrate the capability of IGS to directly connect sequence and structure across length scales from single base pairs to whole organisms.
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.
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