PXD050337

PXD050337 is an original dataset announced via ProteomeXchange.

Title	Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis
Description	Liver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), the release of fibrogenic nano-sized extracellular vesicles (EVs) and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates fibrosis amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition of glycolysis reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated upregulation of EV-related pathways in the liver pericentral zone, which was abrogated by the glycolysis genetic inhibition. Mechanistically, glycolysis in HSCs upregulated the expression of EV-related genes such as RAB31 by enhancing histone-3-lysine-9 acetylation on the promoter region, which increased EV release. Functionally, these glycolysis-dependent EVs increased fibrotic gene expression in recipient HSC. Furthermore, EVs derived from glycolysis-deficient mice abrogated liver fibrosis amplification in contrast to glycolysis-competent mouse EVs. In summary, glycolysis in HSCs amplifies liver fibrosis by promoting fibrogenic EV release in the hepatic pericentral zone, which represents a potential therapeutic target.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:39:33.008.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD050337
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Enis Kostallari
SpeciesList	scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-04 12:43:14	ID requested
1	2024-05-16 14:53:51	announced
⏵ 2	2024-10-22 06:39:33	announced	2024-10-22: Updated project metadata.

10.6019/PXD050337;

submitter keyword: extracellular vesicles,glycolysis, spatial transcriptomics, liver fibrosis, hepatic stellate cells

Enis Kostallari
contact affiliation	Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
contact email	kostallari.enis@mayo.edu
lab head
Enis Kostallari
contact affiliation	Mayo Clinic
contact email	enis.kostallari@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050337
     1. Label: PRIDE project
     2. Name: Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis