ArticleNature metabolism2021
Space-time logic of liver gene expression at sub-lobular scale.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 143 citations in OpenAlex.
- Cell-type-specific circadian and light-responsive transcriptional dynamics in adultProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Haemodynamic control of zonated liver function via instructive vascular Wnt signalling.Nature communications · 2026Article
- Chrono-atlas of cell-type specific daily gene expression rhythms in the regenerating colon.Nature communications · 2026Article
- MASLD: Spatial Mechanisms and New Therapeutics.Biomolecules · 2026Review
- NicheTrans: spatial-aware cross-omics translation.Nature methods · 2026Article
- Single-cell and spatial omics in liver identify cell-cell communication regulators in aging and insulin resistance.Metabolism: clinical and experimental · 2026Article
- Review
- LYNX: a deep generative model for linking spatial dynamics and cell interactions in multimodal spatial data.bioRxiv : the preprint server for biology · 2026Article
- Multi-Omics Landscape of Circadian Clock Dysregulation Across the Chronic Liver Disease Spectrum.International journal of molecular sciences · 2026Review
- Logistic regression for estimating functional effects with spatial transcriptomics.Nucleic acids research · 2026Article
- Reconsidering mammalian circadian organization.Neurobiology of sleep and circadian rhythms · 2026Article
- Article
- [Research advances on hepatocyte zonal changes in metabolic associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Subcellular mRNA localization patterns across tissues resolved with spatial transcriptomics.Nature communications · 2026Article
- Transcriptional noise sets fundamental limits to decoding circadian clock phase from single-cell RNA snapshots.iScience · 2026Article
- Scalable discovery of spatial multicellular patterns via neighborhood-to-sequence transformation.Communications biology · 2026Article
- A novel subset of hepatocytes is simultaneously gluconeogenic andbioRxiv : the preprint server for biology · 2026Article
- Untangling biological complexity: A deep learning approach to separating multiple signals in single-cell data.Cell genomics · 2026Article
- Liver clock: Malalignment and entrainment therapeutics.World journal of gastrointestinal pharmacology and therapeutics · 2026Review
- Loss, amplification or mistiming of the daily rhythms of metabolic markers in patients with cirrhosis.JHEP reports : innovation in hepatology · 2026Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and sub-lobule zones performing distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. However, liver zonation has previously been analysed as a static phenomenon, and liver chronobiology has been analysed at tissue-level resolution. Here, we use single-cell RNA-seq to investigate the interplay between gene regulation in space and time. Using mixed-effect models of messenger RNA expression and smFISH validations, we find that many genes in the liver are both zonated and rhythmic, and most of them show multiplicative space-time effects. Such dually regulated genes cover not only key hepatic functions such as lipid, carbohydrate and amino acid metabolism, but also previously unassociated processes involving protein chaperones. Our data also suggest that rhythmic and localized expression of Wnt targets could be explained by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein. Core circadian clock genes are expressed in a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our scRNA-seq analysis reveals how liver function is compartmentalized spatio-temporally at the sub-lobular scale.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.