PXD016056

PXD016056 is an original dataset announced via ProteomeXchange.

Title	Recovery in the intrinsic myogenic program of congenital myotonic dystrophy myoblasts after excision of the expanded (CTG)n repeat
Description	The congenital form of myotonic dystrophy type 1 (cDM) is caused by large-scale expansion of a (CTG•CAG)n repeat in DMPK and DM1-AS. Production of toxic transcripts with long trinucleotide tracts from these genes results in impediment of myogenic differentiation capacity as cDM’s most prominent morpho-phenotypic hallmark. In the current in vitro study, we compared the early differentiation programs of isogenic cDM myoblasts with and without a (CTG)2600 repeat obtained by gene editing. We found that excision of the repeat restored the ability of cDM myoblasts to engage in myogenic fusion, preventing that the ensuing myotubes remained immature. Although the cDM-typical epigenetic status of the DM1 locus and the expression of genes therein were not altered upon removal of the repeat, analyses at the transcriptome and proteome level revealed that early abnormalities in the temporal expression of differentiation regulators, myogenic progression markers and alternative splicing patterns before and immediately after the onset of differentiation became normalized. Our observation that molecular and cellular features of cDM are reversible and can be corrected by repeat-directed genome editing in muscle progenitors is important information for future development of gene therapy for different forms of DM1.
HostingRepository	PRIDE
AnnounceDate	2019-11-20
AnnouncementXML	Submission_2020-01-14_06:59:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-28 09:35:12	ID requested
1	2019-11-20 00:36:35	announced
⏵ 2	2020-01-14 06:59:13	announced	2020-01-14: Updated publication reference for PubMed record(s): 31766224.

Andr, é LM, van Cruchten RTP, Willemse M, Bezstarosti K, Demmers JAA, van Agtmaal EL, Wansink DG, Wieringa B, Repeat. Int J Mol Sci, 20(22):(2019) [pubmed]

submitter keyword: genome editing, myoblasts, myogenesis, myotonic dystrophy, proteomics, transcriptomics, triplet repeat

Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus MC Rotterdam
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
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/2019/11/PXD016056

PRIDE project URI

• PRIDE
  1. PXD016056
     1. Label: PRIDE project
     2. Name: Recovery in the intrinsic myogenic program of congenital myotonic dystrophy myoblasts after excision of the expanded (CTG)n repeat