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

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-par...

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Autores principales: Qi Su, Sun Y. Kim, Funmi Adewale, Ye Zhou, Christina Aldler, Min Ni, Yi Wei, Michael E. Burczynski, Gurinder S. Atwal, Mark W. Sleeman, Andrew J. Murphy, Yurong Xin, Xiping Cheng
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/0cf76087cfa044fd89ddbc08a3f3891a
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spelling oai:doaj.org-article:0cf76087cfa044fd89ddbc08a3f3891a2021-11-20T05:08:37ZSingle-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver2589-004210.1016/j.isci.2021.103233https://doaj.org/article/0cf76087cfa044fd89ddbc08a3f3891a2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012013https://doaj.org/toc/2589-0042Summary: 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.Qi SuSun Y. KimFunmi AdewaleYe ZhouChristina AldlerMin NiYi WeiMichael E. BurczynskiGurinder S. AtwalMark W. SleemanAndrew J. MurphyYurong XinXiping ChengElsevierarticleAnimal physiologyCell biologyTranscriptomicsScienceQENiScience, Vol 24, Iss 11, Pp 103233- (2021)
institution DOAJ
collection DOAJ
language EN
topic Animal physiology
Cell biology
Transcriptomics
Science
Q
spellingShingle Animal physiology
Cell biology
Transcriptomics
Science
Q
Qi Su
Sun Y. Kim
Funmi Adewale
Ye Zhou
Christina Aldler
Min Ni
Yi Wei
Michael E. Burczynski
Gurinder S. Atwal
Mark W. Sleeman
Andrew J. Murphy
Yurong Xin
Xiping Cheng
Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
description 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.
format article
author Qi Su
Sun Y. Kim
Funmi Adewale
Ye Zhou
Christina Aldler
Min Ni
Yi Wei
Michael E. Burczynski
Gurinder S. Atwal
Mark W. Sleeman
Andrew J. Murphy
Yurong Xin
Xiping Cheng
author_facet Qi Su
Sun Y. Kim
Funmi Adewale
Ye Zhou
Christina Aldler
Min Ni
Yi Wei
Michael E. Burczynski
Gurinder S. Atwal
Mark W. Sleeman
Andrew J. Murphy
Yurong Xin
Xiping Cheng
author_sort Qi Su
title Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
title_short Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
title_full Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
title_fullStr Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
title_full_unstemmed Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
title_sort single-cell rna transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and nafld mouse liver
publisher Elsevier
publishDate 2021
url https://doaj.org/article/0cf76087cfa044fd89ddbc08a3f3891a
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