Cited by 840Genomics and Chromatin DynamicsNuclear Structure and FunctionChromosomal and Genetic Variations

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3D structures of individual mammalian genomes studied by single-cell Hi-C

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Stevens, Tim J., Lando, David, Basu, Srinjan, Atkinson, Liam P., Cao, Yang, Lee, Steven F., Leeb, Martin, Wohlfahrt, Kai J., Boucher, Wayne, O’Shaughnessy-Kirwan, Aoife, Cramard, Julie, Faure, Andre J., Ralser, Meryem, Blanco, Enrique, Morey, Lluis, Sansó, Miriam, Palayret, Matthieu G. S., Lehner, Ben, Di Croce, Luciano, Wutz, Anton, Hendrich, Brian, Klenerman, Dave, Laue, Ernest D.·2017·Nature

DOI 10.1038/nature21429PMC PMC5385134

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Abstract

The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell. By contrast, A and B compartments, lamina-associated domains and active enhancers and promoters are organized in a consistent way on a genome-wide basis in every cell, suggesting that they could drive chromosome and genome folding. By studying genes regulated by pluripotency factor and nucleosome remodelling deacetylase (NuRD), we illustrate how the determination of single-cell genome structure provides a new approach for investigating biological processes.

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Additional file 6 of TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng, Y., Liu, M., Hu, M., & Wang, S. (2021) · Figshare · doi:10.6084/m9.figshare.16960672
Additional file 4 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
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Additional file 5 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
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Additional file 3 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
Li, X., Zeng, G., Li, A., & Zhang, Z. (2021) · Figshare · doi:10.6084/m9.figshare.15058201
Additional file 5 of TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng, Y., Liu, M., Hu, M., & Wang, S. (2021) · Figshare · doi:10.6084/m9.figshare.16960669
Additional file 2 of TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng, Y., Liu, M., Hu, M., & Wang, S. (2021) · Figshare · doi:10.6084/m9.figshare.16960660
Additional file 4 of TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng, Y., Liu, M., Hu, M., & Wang, S. (2021) · Figshare · doi:10.6084/m9.figshare.16960666
Additional file 7 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
Li, X., Zeng, G., Li, A., & Zhang, Z. (2021) · Figshare · doi:10.6084/m9.figshare.15058213
Additional file 3 of TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng, Y., Liu, M., Hu, M., & Wang, S. (2021) · Figshare · doi:10.6084/m9.figshare.16960663
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Self-citation
Additional file 1 of Inferring chromosome radial organization from Hi-C data
Das, P., Shen, T., & McCord, R. P. (2020) · Figshare · doi:10.6084/m9.figshare.13211987
Additional file 8 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
Li, X., Zeng, G., Li, A., & Zhang, Z. (2021) · Figshare · doi:10.6084/m9.figshare.15058216
Additional file 10 of 3D genome organization in the epithelial-mesenchymal transition spectrum
Pang, Q. Y., Tan, T. Z., Sundararajan, V., Chiu, Y.-C., Chee, E. Y. W., Chung, V. Y., Choolani, M. A., & Huang, R. Y.-J. (2022) · Figshare · doi:10.6084/m9.figshare.19930407
Additional file 3 of Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation
Bonora, G., Ramani, V., Singh, R., Fang, H., Jackson, D. L., Srivatsan, S. R., Qiu, R., Lee, C., Trapnell, C., Shendure, J., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16689666
Additional file 2 of Normalization and de-noising of single-cell Hi-C data with BandNorm and scVI-3D
Zheng, Y., Shen, S., & Keleş, S. (2022) · Figshare · doi:10.6084/m9.figshare.21351410
Additional file 1 of TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng, Y., Liu, M., Hu, M., & Wang, S. (2021) · Figshare · doi:10.6084/m9.figshare.16960657
Additional file 2 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
Li, X., Zeng, G., Li, A., & Zhang, Z. (2021) · Figshare · doi:10.6084/m9.figshare.15058195
Additional file 7 of TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Cheng, Y., Liu, M., Hu, M., & Wang, S. (2021) · Figshare · doi:10.6084/m9.figshare.16960675
Additional file 1 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
Li, X., Zeng, G., Li, A., & Zhang, Z. (2021) · Figshare · doi:10.6084/m9.figshare.15058192
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Additional file 2 of 3D genome organization in the epithelial-mesenchymal transition spectrum
Pang, Q. Y., Tan, T. Z., Sundararajan, V., Chiu, Y.-C., Chee, E. Y. W., Chung, V. Y., Choolani, M. A., & Huang, R. Y.-J. (2022) · Figshare · doi:10.6084/m9.figshare.19930413
Additional file 1 of Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation
Bonora, G., Ramani, V., Singh, R., Fang, H., Jackson, D. L., Srivatsan, S. R., Qiu, R., Lee, C., Trapnell, C., Shendure, J., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16689663
Additional file 6 of DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell
Li, X., Zeng, G., Li, A., & Zhang, Z. (2021) · Figshare · doi:10.6084/m9.figshare.15058210
TAD boundaries and gene activity are uncoupled
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Self-citation
Uchimata: a toolkit for visualization of 3D genome structures on the web and in computational notebooks
Kouřil, D., Manz, T., Clarence, T., & Gehlenborg, N. (2026) · Bioinformatics · doi:10.1093/bioinformatics/btag035
“First, we use Stevens et al .’s mouse cell structures (Stevens et al. 2017) and encode each chromosome’s coordinates with a continuous color scale.”
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Fu, Y., Ma, W., Jin, H., Zhang, W., Zhang, S., Chen, Y., Qin, Y., Li, J., Zhai, Z., Li, P., et al. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111236
“Mouse embryonic stem cells (ESCs), serving as in vitro proxies for ICM/epiblast-derived pluripotency, have been instrumental in deciphering the molecular crosstalk between transcription factors, epigenetic modifiers, and 3D genome architecture (9–11).”
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Du, X., Ji, X., Tang, L., & Li, M. (2026) · Big Data Mining and Analytics · doi:10.26599/bdma.2025.9020043
TAD boundary architecture and gene activity are uncoupledPreprint
Almansour, F., Fursova, N. A., Keikhosravi, A., Reed, K. S. M., Larson, D. R., Pegoraro, G., & Misteli, T. (2026) · eLife · doi:10.7554/elife.110197.1
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Peng, Y., Deng, Y., Liu, M., Liu, Z., Li, Y.-H., Zhao, X.-Y., Xing, D., Jia, J., & Ge, H. (2026) · Briefings in Bioinformatics · doi:10.1093/bib/bbag096 · Cited by 1
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Zhu, H., Liu, T., Shrestha, B., & Wang, Z. (2026) · BMC Bioinformatics · doi:10.1186/s12859-026-06421-3
“We executed Nuc_dynamics [6], a 3D chromatin structure modeling tool, to benchmark against SCW using identical chromosomal inputs.”
Influential
TAD boundaries and gene activity are uncoupledPreprint
Almansour, F., Fursova, N. A., Keikhosravi, A., Reed, K. S. M., Larson, D. R., Pegoraro, G., & Misteli, T. (2026) · eLife · doi:10.7554/elife.110197.2
Deciphering X chromosome architecture during mouse preimplantation development
Ranisavljevic, N. (2017) · theses.fr (ABES) · doi:10.70675/08dd1e70z4ea4z4fd1zbcf2z153b2944c2eb
Exploring the structural and functional dynamics of the X-inactivation centre locus during development
Galupa, R. (2017) · theses.fr (ABES) · doi:10.70675/04cc3b8cz6ea7z4c6fzb501z4b35e97f7a72
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3D genome conformation and gene expression in fetal pig muscle at late gestation
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Authors: Stevens, T. J., Lando, D., Basu, S., Atkinson, L. P., Cao, Y., Lee, S. F., Leeb, M., Wohlfahrt, K. J., Boucher, W., O’Shaughnessy-Kirwan, A., Cramard, J., Faure, A. J., Ralser, M., Blanco, E., Morey, L., Sansó, M., Palayret, M. G. S., Lehner, B., Di Croce, L., Wutz, A., Hendrich, B., Klenerman, D., & Laue, E. D.
Affiliations: MRC Laboratory of Molecular Biology (GB)
University of Cambridge (GB)
Wellcome/MRC Cambridge Stem Cell Institute (GB)
European Molecular Biology Laboratory (ES)
Institució Catalana de Recerca i Estudis Avançats (ES)
Corresponding author: Laue, Ernest D.
ORCID: Stevens, Tim J.
Lando, David
Basu, Srinjan
Cao, Yang
Lee, Steven F.
Leeb, Martin
Wohlfahrt, Kai J.
Boucher, Wayne
Cramard, Julie
Blanco, Enrique
Sansó, Miriam
Palayret, Matthieu G. S.
Lehner, Ben
Wutz, Anton
Hendrich, Brian
Laue, Ernest D.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-03-13
Volume: 544
Issue: 7648
Pages: 59-64
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature21429
PMC: PMC5385134
OpenAlex: W2597274540
Cited by: 832
References: 41
Citations by year: 2026: 42 · 2025: 73 · 2024: 62 · 2023: 71 · 2022: 95 · 2021: 115 · 2020: 95 · 2019: 121 · 2018: 99 · 2017: 58
FWCI: 41.56
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Wellcome Trust (082010/Z/07/Z, 277899, 206291/Z/17/Z, 082010)
Medical Research Council (MR/M010082/1, MC_PC_12009, MR/P019471/1)
Cancer Research UK Cambridge Institute, University of Cambridge
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords: 3D genome organization, single-cell Hi-C, chromosome conformation capture, topologically associating domains, chromatin looping, lamina-associated domains, mouse embryonic stem cells, cell-to-cell variability, pluripotency factors, nucleosome remodeling, nuclear organization
MeSH terms: Mouse Embryonic Stem Cells, CCCTC-Binding Factor, Cohesins, Animals, Chromosomal Proteins, Non-Histone, DNA, Enhancer Elements, Genetic, Gene Expression Regulation, Haploidy, Models, Molecular, Molecular Conformation, Nucleosomes, Promoter Regions, Genetic, Repressor Proteins, Reproducibility of Results, G1 Phase, Genome, Cell Cycle Proteins, Chromosomes, Mammalian, Chromatin Assembly and Disassembly, Mice, Gene Regulatory Networks, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Molecular Imaging, Single-Cell Analysis

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3D structures of individual mammalian genomes studied by single-cell Hi-C

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