ArticleAmerican journal of physiology. Endocrinology and metabolism2021
Holistic characterization of single-hepatocyte transcriptome responses to high-fat diet.
Article in American journal of physiology. Endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Rab1A Promotes Hepatic Steatosis by Suppressing Mitophagy via the Raf-1/ERK1/2/PINK1 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Posttranscriptional reprogramming controls MASLD progression through chronic ER stress adaptation.Science advances · 2026Article
- Single cell and single nucleus RNA sequencing in liver tissues: applications and prospects in model and non-model organisms.Frontiers in genetics · 2026Review
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- Hepatic Zonation in MASLD: Old Question, New Challenge in the Era of Spatial Omics.International journal of molecular sciences · 2025Review
- Clinical application of single-cell RNA sequencing in disease and therapy.Clinical and translational medicine · 2025Review
- Review
- Proteomic and phosphoproteomic signatures of aging mouse liver.GeroScience · 2025Article
- Spatial and Single-Cell Transcriptomics Reveals the Regional Division of the Spatial Structure of MASH Fibrosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Liver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.Molecular metabolism · 2024Article
- Study on the Effect of Oleic Acid-Induced Lipogenic Differentiation of Skeletal Muscle Satellite Cells in Yanbian Cattle and Related Mechanisms.Animals : an open access journal from MDPI · 2023Article
- Lack of thyroid hormone receptor beta is not detrimental for non-alcoholic steatohepatitis progression.iScience · 2023Article
- Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.Genome biology · 2023Article
- New discoveries in the field of metabolism by applying single-cell and spatial omics.Journal of pharmaceutical analysis · 2023Review
- Spatial Single-Cell Technologies for Exploring Gastrointestinal Tissue Transcriptome.Comprehensive Physiology · 2023Article
- Effect of an obesogenic high-fat and high-sucrose diet on hepatic gene expression signatures in male Collaborative Cross mice.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Decoding liver fibrogenesis with single-cell technologies.Life medicine · 2022Review
- Article
- Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver.iScience · 2021Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
During nutritional overload and obesity, hepatocyte function is grossly altered, and a subset of hepatocytes begins to accumulate fat droplets, leading to nonalcoholic fatty liver disease (NAFLD). Recent single-cell studies revealed how nonparenchymal cells, such as macrophages, hepatic stellate cells, and endothelial cells, heterogeneously respond to NAFLD. However, it remains to be characterized how hepatocytes, the major constituents of the liver, respond to nutritional overload in NAFLD. Here, using droplet-based, single-cell RNA sequencing (Drop-seq), we characterized how the transcriptomic landscape of individual hepatocytes is altered in response to high-fat diet (HFD) and NAFLD. We showed that the entire hepatocyte population undergoes substantial transcriptome changes upon HFD, although the patterns of alteration were highly heterogeneous, with zonation-dependent and -independent effects. Periportal (zone 1) hepatocytes downregulated many zone 1-specific marker genes, whereas a small number of genes mediating gluconeogenesis were upregulated. Pericentral (zone 3) hepatocytes also downregulated many zone 3-specific genes; however, they upregulated several genes that promote HFD-induced fat droplet formation, consistent with findings that zone 3 hepatocytes accumulate more lipid droplets. Zone 3 hepatocytes also upregulated ketogenic pathways as an adaptive mechanism to HFD. Interestingly, many of the top HFD-induced genes, which encode proteins regulating lipid metabolism, were strongly co-expressed with each other in a subset of hepatocytes, producing a variegated pattern of spatial co-localization that is independent of metabolic zonation. In conclusion, our data set provides a useful resource for understanding hepatocellular alteration during NAFLD at single cell level.
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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.