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Updated: Nov 23, 2025
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Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci
Published on: March 4, 2021
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In situ genome sequencing resolves DNA sequence and structure in intact biological samples
Andrew C Payne1,2, Zachary D Chiang2,3, Paul L Reginato1,2,4,5,6
1Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|January 1, 2021
Summary
In situ genome sequencing (IGS) allows simultaneous DNA sequencing and imaging within cells. This new method reveals genome structure and epigenetic memory in human and mouse embryos.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Understanding genome organization requires integrating DNA sequence with 3D spatial context.
- Current genome-wide methods often lack either base-pair resolution or direct spatial localization.
Purpose of the Study:
- To introduce in situ genome sequencing (IGS), a novel method for simultaneous genome sequencing and imaging within intact biological samples.
- To demonstrate the capability of IGS in characterizing genome structure and epigenetic modifications.
Main Methods:
- Developed and applied in situ genome sequencing (IGS) to human fibroblasts and early mouse embryos.
- Spatially localized thousands of genomic loci within individual nuclei.
- Integrated DNA sequence data with 3D spatial information.
Main Results:
- Characterized parent-specific changes in genome structure during embryonic development.
- Revealed single-cell chromatin domains in zygotes.
- Uncovered epigenetic memory of global chromosome positioning in individual embryos.
Conclusions:
- IGS directly connects DNA sequence and genome structure across various length scales.
- This method provides unprecedented insights into genome organization and epigenetic regulation in single cells.
- IGS has broad applications in developmental biology and understanding genome function.
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