Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis

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The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of ”NASH-associated macrophages” can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH.

OriginalsprogEngelsk
Artikelnummer13484
TidsskriftScientific Reports
Vol/bind12
Udgave nummer1
Antal sider13
ISSN2045-2322
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center, based at the University of Copenhagen, Denmark and partially funded by an unconditional donation from the Novo Nordisk Foundation (NNF18CC0034900). The research was further supported by grants from the Novo Nordisk Foundation (NNF15CC0018486, NNF15OC0016692 and NNF20SA0064142) and the Lundbeck Foundation (R19020143904).

Publisher Copyright:
© 2022, The Author(s).

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