PXD015355

PXD015355 is an original dataset announced via ProteomeXchange.

Title	Myogenesis modelled by human pluripotent stem cells uncovers Duchenne muscular dystrophy phenotypes prior to skeletal muscle commitment
Description	Duchenne muscular dystrophy (DMD) causes severe disability of children and death of young men, with an incidence of approximately 1/5,000 male births. Symptoms appear in early childhood, with a diagnosis made around 4, a time where the amount of muscle damage is already significant, preventing early therapeutic interventions that could be more efficient at halting disease progression. In the meantime, the precise moment at which disease phenotypes arise – even asymptomatically – is still unknown. Thus, there is a critical need to better define DMD onset as well as its first manifestations, which could help identify early disease biomarkers and novel therapeutic targets. In this study, we have used human induced pluripotent stem cells (hiPSCs) from DMD patients to model skeletal myogenesis, and compared their differentiation dynamics to healthy control cells by a comprehensive multi-omics analysis. Transcriptome and miRnome comparisons combined with protein analyses at 7 time points demonstrate that hiPSC differentiation 1) mimics described DMD phenotypes at the differentiation endpoint; and 2) homogeneously and robustly recapitulates key developmental steps - mesoderm, somite, skeletal muscle - which offers the possibility to explore dystrophin functions and find earlier disease biomarkers. Starting at the somite stage, mitochondrial gene dysregulations escalate during differentiation. We also describe fibrosis as an intrinsic feature of skeletal muscle cells that starts early during myogenesis. In sum, our data strongly argue for an early developmental manifestation of DMD whose onset is triggered before the entry into the skeletal muscle compartment, data leading to a necessary reconsideration of dystrophin functions during muscle development.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:26:28.321.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Sweredoski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-09 02:03:38	ID requested
1	2021-09-08 12:01:39	announced
⏵ 2	2024-10-22 05:26:36	announced	2024-10-22: Updated project metadata.

Mournetas V, Massourid, è, s E, Dupont JB, Kornobis E, Polv, è, che H, Jarrige M, Dorval ARL, Gosselin MRF, Manousopoulou A, Garbis SD, G, ó, recki DC, Pinset C, Myogenesis modelled by human pluripotent stem cells: a multi-omic study of Duchenne myopathy early onset. J Cachexia Sarcopenia Muscle, 12(1):209-232(2021) [pubmed]

10.1002/jcsm.12665;

submitter keyword: Human,hiPSCs,Duchenne muscular dystrophy,DMD,TMT

Spiros Garbis
contact affiliation	Proteome Exploration Laboratory, Division of Biology and Biological Engineering, California Institute of Technology
contact email	sgarbis@caltech.edu
lab head
Michael Sweredoski
contact affiliation	Proteome Exploration Laboratory
contact email	msweredo@caltech.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015355
     1. Label: PRIDE project
     2. Name: Myogenesis modelled by human pluripotent stem cells uncovers Duchenne muscular dystrophy phenotypes prior to skeletal muscle commitment