PXD017986

PXD017986 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bio-activation and detoxification
Description	Hepatic organoids are a recent innovation in in vitro modelling. Initial studies suggest organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their propensity for drug metabolism and detoxification remains poorly characterised. A global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was therefore performed to assess both their similarity to liver tissue and DMET expression. iTRAQ analysis revealed 4,405 proteins commonly detected across all sample types. Differentiation of organoids significantly increased the expression of multiple CYP450s, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, they contain multiple DMET proteins necessary for liver function and drug metabolism, such as CYP450 3A, GSTA and MDR1A. Hepatic organoids may therefore represent an attractive novel model for hepatotoxicity testing, although further experimentation, optimisation and characterisation is needed relative to pre-existing models to fully contextualise their use as a putative in vitro model of DILI.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:22:36.270.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rosalind Jenkins
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	methylthiolated residue; iTRAQ8plex-116 reporter+balance reagent acylated residue
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-11 02:45:16	ID requested
1	2021-06-03 08:22:27	announced
⏵ 2	2024-10-22 05:22:37	announced	2024-10-22: Updated project metadata.

10.1007/s00204-021-03075-3;

Howell L, Jenkins RE, Lynch S, Duckworth C, Kevin Park B, Goldring C, Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bioactivation and detoxification. Arch Toxicol, 95(7):2413-2430(2021) [pubmed]

submitter keyword: drug metabolising enzymes and transporters,In vitro, organoid, hepatic phenotype

Rosalind Elspeth Jenkins
contact affiliation	Molecular and Clinical Pharmacology, Centre for Drug Safety Science, University of Liverpool
contact email	R.Jenkins@liv.ac.uk
lab head
Rosalind Jenkins
contact affiliation	University of Liverpool
contact email	R.Jenkins@liv.ac.uk
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/2021/06/PXD017986

PRIDE project URI

• PRIDE
  1. PXD017986
     1. Label: PRIDE project
     2. Name: Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bio-activation and detoxification