Spatial sorting enables comprehensive characterization of liver zonation
Open accessPreprint — published as 10.1038/s42255-019-0109-9 · Paper page
Abstract
The mammalian liver is composed of repeating hexagonal units termed lobules. Spatially-resolved single-cell transcriptomics revealed that about half of hepatocyte genes are differentially expressed across the lobule. Technical limitations impede reconstructing similar global spatial maps of other hepatocyte features. Here, we used zonated surface markers to sort hepatocytes from defined lobule zones with high spatial resolution. We applied transcriptomics, microRNA array measurements and Mass-spectrometry proteomics to reconstruct spatial atlases of multiple zonated hepatocyte features. We found that protein zonation largely overlapped mRNA zonation. We identified zonation of key microRNAs such as miR-122, and inverse zonation of microRNAs and their hepatocyte gene targets, implying potential regulation through zonated mRNA degradation. These targets included the pericentral Wnt receptors Fzd7 and Fzd8 and the periportal Wnt inhibitors Tcf7l1 and Ctnnbip1. Our approach facilitates reconstruction of spatial atlases of multiple cellular features in the liver and in other structured tissues.
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Vandenbon, A., Mizuno, R., Konishi, R., Onishi, M., Masuda, K., Kobayashi, Y., Kawamoto, H., Suzuki, A., He, C., Nakamura, Y., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04479-w · Cited by 12 · see citing works
Fast formation and maturation enhancement of human liver organoids using a liver-organoid-on-a-chip
Byeon, J. H., Jung, D. J., Han, H.-J., Son, W.-C., & Jeong, G. S. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1452485 · Cited by 12 · see citing works
Significance of Liver Zonation in Hepatocellular Carcinoma
Yu, S., Gao, J., Wang, H., Liu, L., Liu, X., Xu, Y., Shi, J., Guo, W., & Zhang, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.806408 · Cited by 12 · see citing works
Unraveling the Complexity of Liver Disease One Cell at a Time
Bader, G. D., McGilvray, I. D., MacParland, S. A., Atif, J., & Thoeni, C. E. (2022) · Seminars in Liver Disease · doi:10.1055/s-0042-1755272 · Cited by 12 · see citing works
- Authors
- Ben-Moshe, S., Shapira, Y., Moor, A. E., Halpern, K. B., & Itzkovitz, S.
- Affiliations
- Weizmann Institute of Science (IL)
- University of Zurich (CH)
- Corresponding author
- Itzkovitz, Shalev
- Venue
- Nature Metabolism
- Publisher
- openRxiv
- Published
- 2019-01-26
- Volume
- 1
- Issue
- 9
- Pages
- 899-911
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC6751089
- OpenAlex
- W2974173934
- Cited by
- 205
- References
- 82
- Citations by year
- 2026: 31 · 2025: 29 · 2024: 42 · 2023: 31 · 2022: 26 · 2021: 26 · 2020: 16 · 2019: 4
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Nature Metabolism (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Digital Access to Libraries (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Howard Hughes Medical Institute (55008734)
- Vallee Foundation
- European Commission (2007–2013, FP7 2007-2013, FP7/2007)
- Weizmann Institute of Science
- Israel Science Foundation (FP7/2007-2013, 1486/16, 1796/12)
- Israeli Centers for Research Excellence (1796/12)
- Planning and Budgeting Committee of the Council for Higher Education of Israel
- FP7 Ideas: European Research Council (335122)
- 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 › Bioinformatics and Genomic Networks
- Keywords
- liver zonation, lobules, spatial sorting, HNF4α, miR-122, mRNA degradation, Wnt signaling, FZD7, FZD8, TCF7L1
- MeSH terms
- Animals, Humans, Liver, RNA, Messenger, Gene Expression Profiling, Protein Transport, Hepatocytes, MicroRNAs, Single-Cell Analysis
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