PXD046701 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Insights from multi-omic modelling of neurodegeneration in Xeroderma Pigmentosum using an induced pluripotent stem cell system |
Description | Xeroderma pigmentosum (XP) is caused by defective nucleotide excision-repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We have identified substantially increased levels of 5',8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents new insights with intervention potential. |
HostingRepository | PRIDE |
AnnounceDate | 2024-04-17 |
AnnouncementXML | Submission_2024-04-17_02:08:56.110.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Graeme Benstead-Hume |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-11-06 06:26:00 | ID requested | |
⏵ 1 | 2024-04-17 02:08:56 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: XP,neurodegeneration |
Contact List
Jyoti Choudhary |
contact affiliation | Functional Proteomics, ICR |
contact email | jyoti.choudhary@icr.ac.uk |
lab head | |
Graeme Benstead-Hume |
contact affiliation | ICR |
contact email | ghume@icr.ac.uk |
dataset submitter | |
Full Dataset Link List
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/2024/04/PXD046701 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046701
- Label: PRIDE project
- Name: Insights from multi-omic modelling of neurodegeneration in Xeroderma Pigmentosum using an induced pluripotent stem cell system