Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis.

Abstract:

:To improve the understanding of the complex biological processes underlying the development of non-alcoholic steatohepatitis (NASH), a multi-omics approach combining bulk RNA-sequencing based transcriptomics, quantitative proteomics and single-cell RNA-sequencing was used to characterize tissue biopsies from histologically validated diet-induced obese (DIO) NASH mice compared to chow-fed controls. Bulk RNA-sequencing and proteomics showed a clear distinction between phenotypes and a good correspondence between mRNA and protein level regulations, apart from specific regulatory events discovered by each technology. Transcriptomics-based gene set enrichment analysis revealed changes associated with key clinical manifestations of NASH, including impaired lipid metabolism, increased extracellular matrix formation/remodeling and pro-inflammatory responses, whereas proteomics-based gene set enrichment analysis pinpointed metabolic pathway perturbations. Integration with single-cell RNA-sequencing data identified key regulated cell types involved in development of NASH demonstrating the cellular heterogeneity and complexity of NASH pathogenesis.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ægidius HM,Veidal SS,Feigh M,Hallenborg P,Puglia M,Pers TH,Vrang N,Jelsing J,Kornum BR,Blagoev B,Rigbolt KTG

doi

10.1038/s41598-020-58059-7

subject

Has Abstract

pub_date

2020-01-24 00:00:00

pages

1148

issue

1

issn

2045-2322

pii

10.1038/s41598-020-58059-7

journal_volume

10

pub_type

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