ArticleExperimental & molecular medicine2017
Dual modulation of human hepatic zonation via canonical and non-canonical Wnt pathways.
Article in Experimental & molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 85 citations in OpenAlex.
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- [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
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- Zone-specific hepatocytes orchestrate the early onset of host immune defenses duringFrontiers in immunology · 2026Article
- Cell type- and species-specific regulation of hepatic lncRNAs by TCDD-activated aryl hydrocarbon receptor.Scientific reports · 2025Article
- Multi-modal analyses of proteomic measurements associated with type 2 diabetes from the Project Baseline Health Study.Communications medicine · 2025Article
- [Biological characteristics of liver zonation and its role in disease and aging].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Rewiring immune evasion in liver metastases: WNT11 as a central node - a mini review.Frontiers in oncology · 2025Review
- Decellularized liver scaffolds for constructing drug-metabolically functionalBioactive materials · 2025Article
- Cell atlas of the regenerating human liver after portal vein embolization.Nature communications · 2024Article
- Development of a human liver microphysiological coculture system for higher throughput chemical safety assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
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- Exploring the Pharmacokinetic Mysteries of the Liver: Application of Series Compartment Models of Hepatic Elimination.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Single-Cell RNA Transcriptome Profiling of Liver Cells of Short-Term Alcoholic Liver Injury in Mice.International journal of molecular sciences · 2023Article
- Long-term cell fate and functional maintenance of human hepatocyte through stepwise culture configuration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Innate immunity and early liver inflammation.Frontiers in immunology · 2023Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The hepatic lobule is divided into three zones along the portal-central vein axis. Hepatocytes within each zone exhibit a distinctive gene expression profile that coordinates their metabolic compartmentalization. The zone-dependent heterogeneity of hepatocytes has been hypothesized to result from the differential degree of exposure to oxygen, nutrition and gut-derived toxins. In addition, the gradient of Wnt signaling that increases towards the central vein seen in rodent models is believed to play a critical role in shaping zonation. Furthermore, hepatic zonation is coupled to the site of the homeostatic renewal of hepatocytes. Despite its critical role, the regulatory mechanisms that determine the distinctive features of zonation and its relevance to humans are not well understood. The present study first conducted a comprehensive zone-dependent transcriptome analysis of normal human liver using laser capture microdissection. Upstream pathway analysis revealed the signatures of host responses to gut-derived toxins in the periportal zone, while both the canonical Wnt pathway and the xenobiotic response pathway govern the perivenular zone. Furthermore, we found that the hypoxic environment of the perivenular zone promotes Wnt11 expression in hepatocytes, which then regulates unique gene expression via activation of the non-canonical Wnt pathway. In summary, our study reports the comprehensive zonation-dependent transcriptome of the normal human liver. Our analysis revealed that the LPS response pathway shapes the characteristics of periportal hepatocytes. By contrast, the perivenular zone is regulated by a combination of three distinct pathways: the xenobiotic response pathway, canonical Wnt signaling, and hypoxia-induced noncanonical Wnt signaling.
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