PXD042227

PXD042227 is an original dataset announced via ProteomeXchange.

Title	One-line-fits-all: a knockdown strategy for rapid, generic and versatile modelling of muscular dystrophies in 3D-tissue-engineered-skeletal-muscle
Description	Humanized 3D-tissue-engineered-skeletal-muscles (3D-TESMs) offer advanced disease modelling, but their application often require isogenic controls and involves laborious and time consuming methodology. Here, by combining 3D-TESM and shRNA approaches, we developed a “one-line-fits-all” disease modelling strategy to rapidly induce distinct genetic deficiencies in a single hiPSC-derived cell line. As proof-of-principle, we recapitulated disease-associated pathology of Duchenne Muscular Dystrophy and LGMD2A caused by loss of function of DMD and CAPN3, respectively. shRNA-mediated knockdown of DMD or CAPN3 induced a loss of contractile function, disruption of tissue architecture, and disease-specific proteomes within a seven days period. Pathology in DMD 3D-TESMs was partially rescued by a candidate gene therapy treatment using microdystrophin, with similar efficacy compared to mouse models. These results show that isogenic shRNA-based humanized 3D-TESM models provide a fast and efficient tool to model muscular dystrophies and are useful for the preclinical evaluation of novel therapies.
HostingRepository	PRIDE
AnnounceDate	2024-02-26
AnnouncementXML	Submission_2024-02-26_12:13:01.495.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lena Keufgens
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-15 04:32:33	ID requested
⏵ 1	2024-02-26 12:13:02	announced

10.1186/s13395-024-00335-5;

In 't Groen SLM, Franken M, Bock T, Kr, ü, ger M, de Greef JC, Pijnappel WWMP, A knock down strategy for rapid, generic, and versatile modelling of muscular dystrophies in 3D-tissue-engineered-skeletal muscle. Skelet Muscle, 14(1):3(2024) [pubmed]

submitter keyword: skeletal-muscle-on-a-chip, disease modelling, 3D-organ-on-a-chip,Duchenne’s muscular dystrophy, dystrophin, LGMD2A, calpain-3, genetic knockdown, tissue engineering

W.W.M. Pim Pijnappel
contact affiliation	1. Department of Clinical Genetics, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands 2. Department of Pediatrics, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands 3. Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands
contact email	w.pijnappel@erasmusmc.nl
lab head
Lena Keufgens
contact affiliation	University of Cologne
contact email	lena.keufgens@uni-koeln.de
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/2024/02/PXD042227

PRIDE project URI

• PRIDE
  1. PXD042227
     1. Label: PRIDE project
     2. Name: One-line-fits-all: a knockdown strategy for rapid, generic and versatile modelling of muscular dystrophies in 3D-tissue-engineered-skeletal-muscle