Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy
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Abstract
Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.
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A single-nucleus RNA sequencing study found differences between 2n and 4n hepatocytes with regards to their expression of genes associated with metabolism, which shows crosstalk with the hepatocyte's position within the lobule.
“Recently, a single-nucleus RNA sequencing study found differences between 2n and 4n hepatocytes with regards to their expression of genes associated with metabolism, which shows crosstalk with the hepatocyte’s position within the lobule.40”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [40]
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Comprehensive study of the murine MASH models' applicability by comparing human liver transcriptomes
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Single-cell analysis of diquat-induced oxidative stress and its impact on organ-specific toxicity
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Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells
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In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene
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Influencing factors and mechanism of hepatocyte regeneration
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Self-citationPloidy inference from single-cell data: application to human and mouse cell atlases
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Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Isolation of Nuclei from Flash-frozen Liver Tissue for Single-cell Multiomics
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Unaltered hepatic wound healing response in male rats with ancestral liver injury
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High-speed cell partitioning through reactive machine learning-guided inkjet printing
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Diploid hepatocytes resist acetaminophen-induced liver injury through suppressed JNK signaling
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Stereo-cell deciphers the spatial and functional heterogeneity of polyploid hepatocytes
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Binucleation ramps up gene expression meeting the physiological demands of an organism
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Allele-specific Effects of Three-dimensional Genome Architecture in Hybrid PigsPreprint
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Allele-specific Effects of Three-dimensional Genome Architecture in Hybrid PigsPreprint
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Self-citationThe liver sinusoid at single-cell level
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Activation and Spatial Redistribution of RNA Splicing Factors Trigger Hepatic Regeneration
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Additional file 8 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 1 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Lanlan, Y., Xu, H., Li, Q.-Y., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652837
Additional file 5 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 13 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 10 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Lanlan, Y., Xu, H., Li, Q.-Y., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652864
Additional file 11 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 12 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Yi, L.-L., Xu, H., Li, Q.-Y., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652870
Additional file 6 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Yi, L.-L., Xu, H., Li, Q., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H.-Y., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652852
Additional file 9 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 4 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Yi, L.-L., Xu, H., Li, Q.-Y., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H.-Y., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652846
Additional file 2 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Yi, L.-L., Xu, H., Li, Q.-Y., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652840
Additional file 7 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Yi, L.-L., Xu, H., Li, Q.-Y., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H.-Y., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652855
Additional file 3 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
Zhu, J., Guan, X., Yi, L.-L., Xu, H., Li, Q.-Y., Cheng, W.-J., Xie, Y., Li, W.-Z., Zhao, H.-Y., Wei, H.-J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26652843
Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution
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Isolation of Mononucleated and Binucleated Hepatocytes by Flow Cytometry
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The Biological Clock–Mitochondria Axis in the Liver: From Molecular Mechanisms to Metabolic Disease
Manuti, V., Murgo, E., Saponaro, A. A., Sfregola, U., Sangineto, M., Villani, R., Serviddio, G., Mazzoccoli, G., & Colangelo, T. (2026) · Biology · doi:10.3390/biology15141197
- Authors
- Richter, M. L., Deligiannis, I. K., Yin, K., Danese, A., Lleshi, E., Coupland, P., Vallejos, C. A., Matchett, K. P., Henderson, N. C., Colome-Tatche, M., & Martinez-Jimenez, C. P.
- Affiliations
- Helmholtz Munich (DE)
- University of Cambridge (GB)
- Western General Hospital (GB)
- Centre for Inflammation Research (GB)
- ORCID
- Venue
- Nature Communications
- Published
- 2021-07-12
- Volume
- 12
- Issue
- 1
- Pages
- 4264-4264
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8275628
- OpenAlex
- W3180187472
- Cited by
- 75
- References
- 141
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 9 · 2023: 21 · 2022: 17 · 2021: 4
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- Site cant be reached (submittedVersion, cc-by)
- Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, other-oa)
- Apollo
- Apollo (cc-by)
- Funders
- Deutsches Krebsforschungszentrum
- Wellcome Trust (219542/Z/19/Z, 219542/Z/19/Z, WT098051, 219542, WT 098051)
- Cancer Research UK (WT098051)
- University of Edinburgh
- European Association for the Study of the Liver
- Cancer Research UK Cambridge Institute, University of Cambridge
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- nuclear transcriptome, hepatocyte ploidy, liver zonation, hepatic lobule, gene dosage, cellular heterogeneity
- MeSH terms
- Animals, Cell Nucleus, Chronic Disease, Frozen Sections, Gene Expression Regulation, Liver, Liver Diseases, Mice, Inbred C57BL, Ploidies, Regeneration, Stem Cells, Transcription Factors, Transcription, Genetic, Biomarkers, Sequence Analysis, RNA, Gene Expression Profiling, Hepatocytes, Mice, Single-Cell Analysis, Gene Ontology
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