PXD045269-1

PXD045269 is an original dataset announced via ProteomeXchange.

Title	Single cell-resolved study of advanced murine NASH reveals quiescence-preserving stellate cell signaling pathways
Description	Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity, insulin resistance, and type II-diabetes and now also known as a leading cause of cirrhosis and hepatocellular carcinoma. Functionally, the NASH liver is compromised by chronic inflammation, microvascular dysfunction, and fibrosis aggravating the initial metabolic derangements. Using single-cell RNA-sequencing, we have here analyzed whole liver plasticity in a murine model of diet-induced, advanced NASH. We analyzed the fibrogenic transition of hepatic stellate cells (HSCs) from pericytes to collagen-producing cells. Stellate cell-specific Gs-protein-coupled receptors and the bile-acid receptor NR1H4/FXR seemingly dominated HSC biology in the healthy liver, forming the basis for multimodal diurnal signaling, but deteriorated in activated HSCs in advanced NASH. Expression of key signaling components were validated in situ in human and murine liver tissue supporting the translatability of our findings and pharmacological relevance in restoration of healthy liver function. We further interrogated the NASH-associated rerouting of mononuclear phagocytes. In addition to two emerging populations of Trem2-expressing monocyte-derived macrophages, we found a population of CD207-positive macrophages significantly expanded in advanced NASH and likely derived from both incoming monocytes and Kupffer cells. We conclude that HSCs of the healthy liver are pivotal for hepatic sensing and integration of postprandial cues, which sustain HSC quiescence and - as inferred from paracrine mediator - overall sinusoidal health. HSC activation driven by parenchymal damage, responding macrophages, and other effectors in the NASH microenvironment is hence not only causally implicated in fibrogenesis but also sinusoidal sensory loss impeding restoration of hepatic homeostasis.
HostingRepository	PRIDE
AnnounceDate	2026-09-01
AnnouncementXML	Submission_2026-09-01_09:37:24.205.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vyacheslav Akimov
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-11 08:09:41	ID requested
⏵ 1	2026-09-01 09:37:24	announced

10.1016/J.JHEP.2023.11.001;

submitter keyword: Pericytes,Fibrosis, Hepatic Stellate Cells., Transcriptomics, Inflammation

Blagoy Blagoev
contact affiliation	Dept. of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
contact email	bab@bmb.sdu.dk
lab head
Vyacheslav Akimov
contact affiliation	Center for Experimental BioInformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
contact email	akimov@bmb.sdu.dk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/09/PXD045269

PRIDE project URI

• PRIDE
  1. PXD045269
     1. Label: PRIDE project
     2. Name: Single cell-resolved study of advanced murine NASH reveals quiescence-preserving stellate cell signaling pathways