Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis
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Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis. / Fred, Rikard G.; Steen Pedersen, Julie; Thompson, Jonatan J.; Lee, Julie; Timshel, Pascal N.; Stender, Stefan; Rygg, Marte Opseth; Gluud, Lise Lotte; Bjerregaard Kristiansen, Viggo; Bendtsen, Flemming; Hansen, Torben; Pers, Tune H.
I: Scientific Reports, Bind 12, Nr. 1, 13484, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis
AU - Fred, Rikard G.
AU - Steen Pedersen, Julie
AU - Thompson, Jonatan J.
AU - Lee, Julie
AU - Timshel, Pascal N.
AU - Stender, Stefan
AU - Rygg, Marte Opseth
AU - Gluud, Lise Lotte
AU - Bjerregaard Kristiansen, Viggo
AU - Bendtsen, Flemming
AU - Hansen, Torben
AU - Pers, Tune H.
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-022-16754-7
DO - 10.1038/s41598-022-16754-7
M3 - Journal article
C2 - 35931712
AN - SCOPUS:85135496305
VL - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 13484
ER -
ID: 318032374