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

Rikard G Fred, Julie Steen Pedersen, Jonatan J Thompson, Julie Lee, Pascal N Timshel, Stefan Stender, Marte Opseth Rygg, Lise Lotte Gluud, Viggo Bjerregaard Kristiansen, Flemming Bendtsen, Torben Hansen, Tune H Pers

Abstract

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.

Original languageEnglish
Article number13484
JournalScientific Reports
Volume12
Issue number1
Pages (from-to)1-13
Number of pages13
ISSN2045-2322
DOIs
Publication statusPublished - 5 Aug 2022

Keywords

  • Biomarkers/metabolism
  • Fibrosis
  • Genome-Wide Association Study
  • Humans
  • Liver/metabolism
  • Non-alcoholic Fatty Liver Disease/pathology
  • Transcriptome

Fingerprint

Dive into the research topics of 'Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis'. Together they form a unique fingerprint.

Cite this