RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing.
Journal
HGG advances
ISSN: 2666-2477
Titre abrégé: HGG Adv
Pays: United States
ID NLM: 101772885
Informations de publication
Date de publication:
13 Jan 2022
13 Jan 2022
Historique:
received:
12
02
2021
accepted:
18
08
2021
entrez:
20
1
2022
pubmed:
21
1
2022
medline:
21
1
2022
Statut:
epublish
Résumé
Urinary stem cells (USCs) are a non-invasive, simple, and affordable cell source to study human diseases. Here we show that USCs are a versatile tool for studying Duchenne muscular dystrophy (DMD), since they are able to address RNA signatures and atypical mutation identification. Gene expression profiling of DMD individuals' USCs revealed a profound deregulation of inflammation, muscle development, and metabolic pathways that mirrors the known transcriptional landscape of DMD muscle and worsens following USCs' myogenic transformation. This pathogenic transcription signature was reverted by an exon-skipping corrective approach, suggesting the utility of USCs in monitoring DMD antisense therapy. The full DMD transcript profile performed in USCs from three undiagnosed DMD individuals addressed three splicing abnormalities, which were decrypted and confirmed as pathogenic variations by whole-genome sequencing (WGS). This combined genomic approach allowed the identification of three atypical and complex
Identifiants
pubmed: 35047845
doi: 10.1016/j.xhgg.2021.100054
pii: S2666-2477(21)00035-X
pmc: PMC8756543
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100054Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
A.F. is the Principal Investigator of Sarepta Therapeutics Essence and MIS51ON clinical trial for DMD. A.F. is PI of ongoing grants on DMD diagnosis funded by PTC Therapeutics and Sarepta Therapeutics. All other authors declare no competing interests.
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