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

Research output: Contribution to journalJournal articleResearchpeer-review

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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.

In: Scientific Reports, Vol. 12, No. 1, 13484, 2022.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Fred, RG, Steen Pedersen, J, Thompson, JJ, Lee, J, Timshel, PN, Stender, S, Rygg, MO, Gluud, LL, Bjerregaard Kristiansen, V, Bendtsen, F, Hansen, T & Pers, TH 2022, 'Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis', Scientific Reports, vol. 12, no. 1, 13484. https://doi.org/10.1038/s41598-022-16754-7

APA

Fred, R. G., Steen Pedersen, J., Thompson, J. J., Lee, J., Timshel, P. N., Stender, S., Rygg, M. O., Gluud, L. L., Bjerregaard Kristiansen, V., Bendtsen, F., Hansen, T., & Pers, T. H. (2022). Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis. Scientific Reports, 12(1), [13484]. https://doi.org/10.1038/s41598-022-16754-7

Vancouver

Fred RG, Steen Pedersen J, Thompson JJ, Lee J, Timshel PN, Stender S et al. Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis. Scientific Reports. 2022;12(1). 13484. https://doi.org/10.1038/s41598-022-16754-7

Author

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. / Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis. In: Scientific Reports. 2022 ; Vol. 12, No. 1.

Bibtex

@article{ccc594c520d24a2fa028108704a014af,
title = "Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis",
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.",
author = "Fred, {Rikard G.} and {Steen Pedersen}, Julie and Thompson, {Jonatan J.} and Julie Lee and Timshel, {Pascal N.} and Stefan Stender and Rygg, {Marte Opseth} and Gluud, {Lise Lotte} and {Bjerregaard Kristiansen}, Viggo and Flemming Bendtsen and Torben Hansen and Pers, {Tune H.}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41598-022-16754-7",
language = "English",
volume = "12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

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