PXD061287

PXD061287 is an original dataset announced via ProteomeXchange.

Title	Integrated single cell functional-proteomic profiling of human skeletal muscle reveals a shift in cellular specificity in nemaline myopathy
Description	Skeletal muscle is a complex syncytial arrangement of an array of cell types and, in the case of muscle specific cells (myofibers), sub-types. There exists extensive heterogeneity in skeletal muscle functional behaviour and molecular landscape, at the cell composition, myofiber sub-type and intra-myofiber sub-type level. This heterogeneity highlights limitations in currently applied methodological approaches, which has stagnated our understanding of fundamental skeletal muscle biology in both healthy and myopathic contexts. Here, we developed a novel approach that combines a fluorescence based assay for the biophysical examination of the sarcomeric protein, myosin, coupled with same-myofiber high sensitivity proteome profiling, termed Single Myofiber Protein Function-Omics (SMPFO). Successfully applying this approach to healthy human skeletal muscle tissue, we identify the integrate relationship between myofiber functionality and the underlying proteomic landscape that guides divergent, but physiologically important, behaviour in myofiber sub-types. By applying SMPFO to two forms of human nemaline myopathy (ACTA1 and TNNT1 mutations), we reveal significant reduction in the divergence of myofiber sub-types, across both biophysical and proteomic behaviour. Collectively, we develop SMPFO as a novel approach to study skeletal muscle with greater specificity, accuracy and resolution then currently applied methods, facilitating that advancement in understanding of SkM tissue in both healthy and diseased states.
HostingRepository	PRIDE
AnnounceDate	2025-06-09
AnnouncementXML	Submission_2025-06-08_16:44:54.886.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roger Moreno Justicia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-27 15:43:30	ID requested
⏵ 1	2025-06-08 16:44:55	announced

10.1113/jp288363;

Seaborne RAE, Moreno-Justicia R, Laitila J, Lewis CTA, Savoure L, Zanoteli E, Lawlor MW, Jungbluth H, Deshmukh AS, Ochala J, Integrated single-cell functional-proteomic profiling reveals a shift in myofibre specificity in human nemaline myopathy: A proof-of-principle study. J Physiol, 603(10):3033-3048(2025) [pubmed]

submitter keyword: protein function-omics, nemaline myopathy,single muscle fiber

Atul Shahaji Deshmukh
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research University of Copenhagen, Denmark
contact email	atul.deshmukh@sund.ku.dk
lab head
Roger Moreno Justicia
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research
contact email	roger.moreno.justicia@sund.ku.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/2025/06/PXD061287

PRIDE project URI

• PRIDE
  1. PXD061287
     1. Label: PRIDE project
     2. Name: Integrated single cell functional-proteomic profiling of human skeletal muscle reveals a shift in cellular specificity in nemaline myopathy