In situ genome sequencing resolves DNA sequence and structure in intact biological samples.

IF: 63.714

Cited by: 117

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.

Keywords

ISS

3D-FISH

FISSEQ

ExSeq

Spatial Genomics

MeSH terms

Animals

Base Sequence

Cell Nucleus

Chromatin

Chromosome Positioning

Chromosomes, Human

Chromosomes, Mammalian

Embryo, Mammalian

Embryonic Development

Epigenesis, Genetic

Fibroblasts

Genome

Genome, Human

High-Throughput Nucleotide Sequencing

Humans

Mice

Sequence Analysis, DNA

Single-Cell Analysis

Spatial Analysis

Authors

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

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