Apr 18, 2020

Holistic Characterization of Single Hepatocyte Transcriptome Responses to High Fat Diet

BioRxiv : the Preprint Server for Biology
S.-R. ParkJun Hee Lee

Abstract

During nutritional overload and obesity, hepatocyte function is grossly altered, and a subset of hepatocytes begins to accumulate fat droplets, leading to non-alcoholic fatty liver disease (NAFLD). Recent single cell studies revealed how non-parenchymal 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 entire hepatocytes 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, while 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 ...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Meta-Analysis (Publications)
Meta Analysis (Statistical Procedure)
Genes
Virus Replication
Etiology
Gene Expression
Serine
Gene Mutant
Gene Mapping, Human

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