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Single-cell Hi-C reveals cell-to-cell variability in chromosome structure
Open accessAbstract
Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single-cell Hi-C, combined with genome-wide statistical analysis and structural modelling of single-copy X chromosomes, to show that individual chromosomes maintain domain organization at the megabase scale, but show variable cell-to-cell chromosome structures at larger scales. Despite this structural stochasticity, localization of active gene domains to boundaries of chromosome territories is a hallmark of chromosomal conformation. Single-cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organization underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns.
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In the citing paper
“Some types of epigenetic modifications, such as changes in chromosome conformation are still largely unexplored in MDD.414,415”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [414]
Experimental — accuracy not yet measuredIn the citing paper
“Similarly, single-cell Hi-C can derive a coherent three-dimensional chromosomal topology29 unattainable from bulk 3C data, which averages the chromosomal conformations in millions of cells.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [29]
In the citing paper
“In our previous version of the single-cell Hi-C protocol12 we found that molecules supported by a single read (singleton contacts) usually represented spurious ligations and were therefore discarded.”
From Cell-cycle dynamics of chromosomal organization at single-cell resolution (2017) · cites this paper as [12]
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Metadata
- Authors
- Nagano, T., Lubling, Y., Stevens, T. J., Schoenfelder, S., Yaffe, E., Dean, W., Laue, E. D., Tanay, A., & Fraser, P.
- Affiliations
- Babraham Institute (GB)
- Weizmann Institute of Science (IL)
- University of Cambridge (GB)
- Corresponding author
- Laue, Ernest D.
- Tanay, Amos
- Fraser, Peter
- ORCID
- Venue
- Nature
- Published
- 2013-09-25
- Volume
- 502
- Issue
- 7469
- Pages
- 59-64
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3869051
- OpenAlex
- W1965863160
- Cited by
- 1,589
- References
- 32
- Citations by year
- 2026: 75 · 2025: 100 · 2024: 118 · 2023: 115 · 2022: 120 · 2021: 177 · 2020: 132 · 2019: 143 · 2018: 147 · 2017: 126 · 2016: 116 · 2015: 125 · 2014: 86 · 2013: 8
- FWCI
- 50.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council (BBS/E/B/0000M241, BBS/E/B/000C0404, BBS/E/B/0000C151)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- single-cell Hi-C, chromosome conformation, cell-to-cell variability, chromosome structure, chromosome territories, X chromosome, 3D genome organization, chromatin interactions, interdomain contacts, nuclear organization
- MeSH terms
- Animals, Cell Nucleus, Chromatin, Chromosomes, Genetic Techniques, Male, Models, Molecular, Molecular Conformation, X Chromosome, Mice, Single-Cell Analysis
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