1. Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
- Author
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Yurong Xin, Xiping Cheng, Christina Aldler, Qi Su, Andrew J. Murphy, Michael E. Burczynski, Ye Zhou, Gurinder S. Atwal, Funmi Adewale, Min Ni, Mark W. Sleeman, Sun Y. Kim, and Yi Wei
- Subjects
Regulation of gene expression ,Cell biology ,Multidisciplinary ,Science ,Cell ,Biology ,medicine.disease ,digestive system ,Article ,Transcriptome ,Pathogenesis ,Immune system ,medicine.anatomical_structure ,Nonalcoholic fatty liver disease ,Animal physiology ,Cancer research ,Hepatic stellate cell ,medicine ,Transcriptomics ,Myofibroblast - Abstract
Summary Nonalcoholic fatty liver disease (NAFLD) is a global health-care problem with limited therapeutic options. To obtain a cellular resolution of pathogenesis, 82,168 single-cell transcriptomes (scRNA-seq) across different NAFLD stages were profiled, identifying hepatocytes and 12 other non-parenchymal cell (NPC) types. scRNA-seq revealed insights into the cellular and molecular mechanisms of the disease. We discovered a dual role for hepatic stellate cells in gene expression regulation and in the potential to trans-differentiate into myofibroblasts. We uncovered distinct expression profiles of Kupffer cells versus monocyte-derived macrophages during NAFLD progression. Kupffer cells showed stronger immune responses, while monocyte-derived macrophages demonstrated a capability for differentiation. Three chimeric NPCs were identified including endothelial-chimeric stellate cells, hepatocyte-chimeric endothelial cells, and endothelial-chimeric Kupffer cells. Our work identified unanticipated aspects of mouse with NAFLD at the single-cell level and advanced the understanding of cellular heterogeneity in NAFLD livers., Graphical abstract, Highlights • Of all, 82,168 single-cell transcriptomes across different NAFLD stages were profiled • Hepatocytes and 12 non-parenchymal cell types were identified in mouse liver • Three chimeric NPCs were identified in mouse liver, Animal physiology; Cell biology; Transcriptomics
- Published
- 2021