Abstract:
:Facioscapulohumeral muscular dystrophy (FSHD) is an incurable disorder linked to ectopic expression of DUX4. However, DUX4 is notoriously difficult to detect in FSHD muscle cells, while DUX4 target gene expression is an inconsistent biomarker for FSHD skeletal muscle biopsies, displaying efficacy only on pathologically inflamed samples. Immune gene misregulation occurs in FSHD muscle, with DUX4 target genes enriched for those associated with inflammatory processes. However, there lacks an assessment of the FSHD immune cell transcriptome, and its contribution to gene expression in FSHD muscle biopsies. Here, we show that EBV-immortalized FSHD lymphoblastoid cell lines express DUX4 and both early and late DUX4 target genes. Moreover, a biomarker of 237 up-regulated genes derived from FSHD lymphoblastoid cell lines is elevated in FSHD muscle biopsies compared to controls. The FSHD Lymphoblast score is unaltered between FSHD myoblasts/myotubes and their controls however, implying a non-myogenic cell source in muscle biopsies. Indeed, the FSHD Lymphoblast score correlates with the early stages of muscle inflammation identified by histological analysis on muscle biopsies, while our two late DUX4 target gene expression biomarkers associate with macroscopic inflammation detectable via MRI. Thus, FSHD lymphoblastoid cell lines express DUX4 and early and late DUX4 target genes, therefore, muscle-infiltrated immune cells may contribute the molecular landscape of FSHD muscle biopsies.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Banerji CRS,Panamarova M,Zammit PSdoi
10.1093/hmg/ddaa053subject
Has Abstractpub_date
2020-08-11 00:00:00pages
2285-2299issue
14eissn
0964-6906issn
1460-2083pii
5815186journal_volume
29pub_type
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