ArticleNature cell biology2024
Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 67 citations in OpenAlex.
- Integrated single-cell multiomics reveals neutrophil-driven immune-metabolic reprogramming of Kupffer cells via thrombospondin-1/CD36 after surgical stress.JCI insight · 2026Article
- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- Predictive design of tissue-specific mammalian enhancers that function in the mouse embryo.Nature genetics · 2026Article
- Systematic comparison of estimates of transcription factor activity by ATAC-seq and multiplexed reporter assays.Molecular systems biology · 2026Article
- Leveraging IGF signaling to improve the spatial organization and regenerative potential of iPSC-derived vascularized liver organoids.Science advances · 2026Article
- Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Hypoxia in MASLD: a spatial determinant of the pathogenesis.Trends in molecular medicine · 2026Review
- Article
- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- Advancing AI for multi-omics and clinical data integration in basic and translational cancer research.Nature reviews. Cancer · 2026Review
- Interpretable spatial multi-omics data integration and dimensionality reduction with SpaMV.Nature communications · 2026Article
- EasySCP unveils extensive liver zonation at single-cell proteomics resolution.Nature communications · 2026Article
- Differential Wnt/β-catenin signaling via TCF7L2/LEF1 binding specificity shapes cellular and tumor phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- MetaNet: a scalable and integrated tool for reproducible omics network analysis.Bioinformatics (Oxford, England) · 2026Article
- Challenges in predicting chromatin accessibility differences between species.NAR genomics and bioinformatics · 2026Article
- Article
- SAA/FPR2 Signaling Between Pericentral Hepatocytes and Macrophages Exacerbates Zonated Liver Transplant Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Predicting enhancer-gene links from single-cell multi-omics data by integrating prior Hi-C information.Nucleic acids research · 2026Article
- CREsted: modeling genomic and synthetic cell-type-specific enhancers across tissues and species.Nature methods · 2026Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
In the mammalian liver, hepatocytes exhibit diverse metabolic and functional profiles based on their location within the liver lobule. However, it is unclear whether this spatial variation, called zonation, is governed by a well-defined gene regulatory code. Here, using a combination of single-cell multiomics, spatial omics, massively parallel reporter assays and deep learning, we mapped enhancer-gene regulatory networks across mouse liver cell types. We found that zonation affects gene expression and chromatin accessibility in hepatocytes, among other cell types. These states are driven by the repressors TCF7L1 and TBX3, alongside other core hepatocyte transcription factors, such as HNF4A, CEBPA, FOXA1 and ONECUT1. To examine the architecture of the enhancers driving these cell states, we trained a hierarchical deep learning model called DeepLiver. Our study provides a multimodal understanding of the regulatory code underlying hepatocyte identity and their zonation state that can be used to engineer enhancers with specific activity levels and zonation patterns.
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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.