Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver

Su, Q, Kim, SY, Adewale, F, Zhou, Y, Aldler, C, Ni, M, Wei, Y, Burczynski, ME, Atwal, GS, Sleeman, MW, Murphy, AJ, Xin, Y, Cheng, X (November 2021) Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver. iScience, 24 (11). p. 103233. ISSN 2589-0042

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DOI: 10.1016/j.isci.2021.103233


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.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > organs types and functions > liver
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:
Communities: CSHL labs > Atwal lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 19 November 2021
Date Deposited: 27 Jan 2022 14:31
Last Modified: 27 Jan 2022 14:31

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