PXD025691

PXD025691 is an original dataset announced via ProteomeXchange.

Title	Fibrosis-activated transcriptional networks govern hepatocyte reprogramming and intra-hepatic communication in metabolic associated liver fibrosis
Description	Liver fibrosis is a strong predictor of long-term mortality in patients with non-alcoholic fatty liver disease; yet the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely under-stood. Using a cell type-resolved genomics approach, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a partial loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a net-work of NASH-activated transcription factors (TFs), as exemplified by Elf3 and Glis2. Indeed, Elf3 and Glis2 controlled hepatocyte identity and fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell (HSC) gene programs. Thus, interconnected TF networks not only promoted hepatocyte dysfunction, but also directed the intra-hepatic crosstalk with HSCs necessary for NASH and fibrosis progression implying molecular “hub-centered” targeting strategies to be superior to existing mono-target approaches as currently used in NASH therapy.
HostingRepository	PRIDE
AnnounceDate	2021-07-13
AnnouncementXML	Submission_2021-07-12_22:10:34.485.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michele Puglia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-28 03:43:43	ID requested
⏵ 1	2021-07-12 22:10:35	announced

Loft A, Alfaro AJ, Schmidt SF, Pedersen FB, Terkelsen MK, Puglia M, Chow KK, Feuchtinger A, Troullinaki M, Maida A, Wolff G, Sakurai M, Berutti R, Ekim , Ü, st, ü, nel B, Nawroth P, Ravnskjaer K, Diaz MB, Blagoev B, Herzig S, Liver-fibrosis-activated transcriptional networks govern hepatocyte reprogramming and intra-hepatic communication. Cell Metab, 33(8):1685-1700.e9(2021) [pubmed]

submitter keyword: NASH, PRM, Elf3, Glis2, MOUSE, Exploris 480, Liver fibrosis

Blagoy Blagoev
contact affiliation	Department of Biochemistry and Molecular Biology; University of Southern Denmark; Odense; 5230; Denmark
contact email	bab@bmb.sdu.dk
lab head
Michele Puglia
contact affiliation	University of Southern Denmark
contact email	michelep@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/2021/07/PXD025691

PRIDE project URI

• PRIDE
  1. PXD025691
     1. Label: PRIDE project
     2. Name: Fibrosis-activated transcriptional networks govern hepatocyte reprogramming and intra-hepatic communication in metabolic associated liver fibrosis