In Situ Genome Sequencing Resolves DNA Sequence and Structure in Intact Biological Samples

Overview

Journal Science

Specialty Science

Date 2021 Jan 1

PMID 33384301

Citations 97

Authors

Andrew C Payne

Zachary D Chiang

Paul L Reginato

Sarah M Mangiameli

Evan M Murray

Chun-Chen Yao

Styliani Markoulaki

Andrew S Earl

Ajay S Labade

Rudolf Jaenisch

George M Church

Edward S Boyden

Jason D Buenrostro

Fei Chen

Affiliations

Soon will be listed here.

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.

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