DUX4 expressing immortalized FSHD lymphoblastoid cells express genes elevated in FSHD muscle biopsies, correlating with the early stages of inflammation
| Autor: | Peter S. Zammit, Maryna Panamarova, Christopher R. S. Banerji |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Male AcademicSubjects/SCI01140 congenital hereditary and neonatal diseases and abnormalities Biopsy Biology Cell Line Transcriptome 03 medical and health sciences 0302 clinical medicine DUX4 Genetics medicine Facioscapulohumeral muscular dystrophy Myocyte Humans Muscle Skeletal Molecular Biology Genetics (clinical) Homeodomain Proteins Inflammation Muscle Cells Myogenesis Lymphoblast Skeletal muscle General Medicine medicine.disease Magnetic Resonance Imaging Muscular Dystrophy Facioscapulohumeral nervous system diseases 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Cancer research Ectopic expression Female General Article 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Human Molecular Genetics |
| ISSN: | 1460-2083 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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