PXD046863

PXD046863 is an original dataset announced via ProteomeXchange.

Title	Beyond Myosin Heavy Chains in Human Skeletal Muscle Heterogeneity
Description	Skeletal muscle is an inherently heterogenous tissue comprised primarily of myofibers, which are historically classified into three distinct fiber types in humans: one “slow” (type 1) and two “fast” (type 2A and type 2X), delineated by the expression of myosin heavy chain isoforms (MYHs). However, whether discrete fiber types exist or whether fiber heterogeneity reflects a continuum remains unclear. Furthermore, whether MYHs are the main classifiers of skeletal muscle fibers has not been examined in an unbiased manner. Through the development and application of novel transcriptomic and proteomic workflows, applied to 1050 and 1038 single muscle fibers from human vastus lateralis, respectively, we show that MYHs are not the principal drivers of skeletal muscle fiber heterogeneity. Instead, ribosomal heterogeneity drives the majority of variance between skeletal muscle fibers in a continual fashion, independent of slow/fast fiber type. Furthermore, whilst slow and fast fiber clusters can be identified, described by their contractile and metabolic profiles, our data challenge the concept that type 2X are phenotypically distinct from other fast fibers at an omics level. Moreover, MYH-based classifications do not adequately describe the phenotype of skeletal muscle fibers in one of the most common genetic muscle diseases, nemaline myopathy. Our data question the currently accepted model of multiple distinct fiber types based on the expression of MYHs in humans and identifies ribosomal heterogeneity as a major driver of skeletal muscle fiber heterogeneity, opening a new field of research within skeletal muscle physiology.
HostingRepository	PRIDE
AnnounceDate	2025-05-09
AnnouncementXML	Submission_2025-05-09_00:07:51.190.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 SCP

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-11 05:56:27	ID requested
⏵ 1	2025-05-09 00:07:52	announced

10.1038/s41467-025-56896-6;

Moreno-Justicia R, Van der Stede T, Stocks B, Laitila J, Seaborne RA, Van de Loock A, Lievens E, Samodova D, Mar, í, n-Arraiza L, Dmytriyeva O, Browaeys R, Van Vossel K, Moesgaard L, Yigit N, Anckaert J, Weyns A, Van Thienen R, Sahl RE, Zanoteli E, Lawlor MW, Wierer M, Mestdagh P, Vandesompele J, Ochala J, Hostrup M, Derave W, Deshmukh AS, Human skeletal muscle fiber heterogeneity beyond myosin heavy chains. Nat Commun, 16(1):1764(2025) [pubmed]

submitter keyword: Single muscle fiber

cell heterogeneity

myopathy

fiber type

Atul Shahaji
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research
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/2025/02/PXD046863

PRIDE project URI

• PRIDE
  1. PXD046863
     1. Label: PRIDE project
     2. Name: Beyond Myosin Heavy Chains in Human Skeletal Muscle Heterogeneity