PXD019060

PXD019060 is an original dataset announced via ProteomeXchange.

Title	Protein signature of human skin fibroblasts indicates the suitability to serve as in vitro model for neuromuscular diseases (Library 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_06:28:19.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

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-08 05:52:04	ID requested
⏵ 1	2020-11-10 06:28:19	announced

Dataset with its publication pending

submitter keyword: Allgrove syndrome, Aladin, AAAS, triple-A syndrome, Myopodin/Synaptopodin-2, Ataxin-2

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

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PRIDE project URI

• PRIDE
  1. PXD019060
     1. Label: PRIDE project
     2. Name: Protein signature of human skin fibroblasts indicates the suitability to serve as in vitro model for neuromuscular diseases (Library Data)