PXD019201 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Protein signature of human skin fibroblasts indicates the suitability to serve as in vitro model for neuromuscular diseases (AAAS-Data) |
Description | The elucidation of pathomechanisms leading to the manifestation of neuromuscular diseases (NMDs) represents an important step toward the understanding of the genesis of the respective disease and might help to define starting points for (new) therapeutic intervention concepts. However, these “discovery studies” are often limited by the availability of human biomaterial especially regarding the fact that muscle and nerve biopsies became less common in the diagnostic work-up of patients suffering from NMDs. Moreover, given that results of next-generation-sequencing approaches frequently result in the identification of ambiguous variants, testing of their pathogenicity is crucial but also depending on patient-derived material. To systematically address the question if human skin fibroblasts might serve as a valuable biomaterial for (molecular) studies of NMDs, using proteomic profiling we generated a protein library by decreasing protein complexity via pH8-based sample fractionation: cataloguing of 8280 proteins revealed the expression of a variety of such linked to genetic forms of motor neuron diseases, congenital myasthenic syndromes, neuropathies and muscular disorders. In silico-based pathway analyses revealed expression of a variety of proteins involved in muscle contraction and such decisive for neuronal function and maintenance suggesting the suitability of human skin fibroblasts to study the etiology of NMDs. Based on these findings, next we aimed to further demonstrate the suitability of this in vitro model to study NMDs by a use case: utilizing a data independent acquisition (DIA) approach, the proteomic signature of whole protein extracts of fibroblasts derived from an Allgrove-patient was studied. Paradigmatic dysregulated proteins were confirmed in muscle biopsy of the patient and protein-functions could be linked to neurological symptoms known for this disease. Moreover, LC-MS/MS-based investigation of nuclear protein composition allowed the identification of protein-dysregulations which accord with structural perturbations observed in the muscle biopsy. |
HostingRepository | PRIDE |
AnnounceDate | 2020-11-10 |
AnnouncementXML | Submission_2020-11-10_06:24:57.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Andreas Hentschel |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-05-14 06:01:45 | ID requested | |
⏵ 1 | 2020-11-10 06:24:57 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Allgrove syndrome, Aladin, AAAS, triple-A syndrome, Myopodin/Synaptopodin-2, Ataxin-2 |
Contact List
Andreas Hentschel |
contact affiliation | Bioanalytics, Leibnizinstitut für analytische Wissenschaften-ISAS-e.V., Germany |
contact email | Andreas.hentschel@isas.de |
lab head | |
Andreas Hentschel |
contact affiliation | Leibniz Institut für Analytische Wissenschaften |
contact email | andreas.hentschel@isas.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019201
- Label: PRIDE project
- Name: Protein signature of human skin fibroblasts indicates the suitability to serve as in vitro model for neuromuscular diseases (AAAS-Data)