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Facioscapulohumeral dystrophy transcriptome signatures correlate with different stages of disease and are marked by different MRI biomarkers.
- Source :
-
Scientific reports [Sci Rep] 2022 Jan 26; Vol. 12 (1), pp. 1426. Date of Electronic Publication: 2022 Jan 26. - Publication Year :
- 2022
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Abstract
- With several therapeutic strategies for facioscapulohumeral muscular dystrophy (FSHD) entering clinical testing, outcome measures are becoming increasingly important. Considering the spatiotemporal nature of FSHD disease activity, clinical trials would benefit from non-invasive imaging-based biomarkers that can predict FSHD-associated transcriptome changes. This study investigated two FSHD-associated transcriptome signatures (DUX4 and PAX7 signatures) in FSHD skeletal muscle biopsies, and tested their correlation with a variety of disease-associated factors, including Ricci clinical severity score, disease duration, D4Z4 repeat size, muscle pathology scorings and functional outcome measures. It establishes that DUX4 and PAX7 signatures both show a sporadic expression pattern in FSHD-affected biopsies, possibly marking different stages of disease. This study analyzed two imaging-based biomarkers-Turbo Inversion Recovery Magnitude (TIRM) hyperintensity and fat fraction-and provides insights into their predictive power as non-invasive biomarkers for FSHD signature detection in clinical trials. Further insights in the heterogeneity of-and correlation between-imaging biomarkers and molecular biomarkers, as provided in this study, will provide important guidance to clinical trial design in FSHD. Finally, this study investigated the role of infiltrating non-muscle cell types in FSHD signature expression and detected potential distinct roles for two fibro-adipogenic progenitor subtypes in FSHD.<br /> (© 2022. The Author(s).)
- Subjects :
- Biomarkers metabolism
Biopsy
Case-Control Studies
Female
Gene Expression Profiling
Gene Expression Regulation
Homeodomain Proteins metabolism
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Muscle, Skeletal diagnostic imaging
Muscle, Skeletal pathology
Muscular Dystrophy, Facioscapulohumeral diagnostic imaging
Muscular Dystrophy, Facioscapulohumeral metabolism
Muscular Dystrophy, Facioscapulohumeral pathology
PAX7 Transcription Factor metabolism
Severity of Illness Index
Stem Cells metabolism
Stem Cells pathology
Homeodomain Proteins genetics
Muscle, Skeletal metabolism
Muscular Dystrophy, Facioscapulohumeral genetics
PAX7 Transcription Factor genetics
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 35082321
- Full Text :
- https://doi.org/10.1038/s41598-022-04817-8