Related Experiment Video
Updated: May 31, 2026
Studying Muscle Transcriptional Dynamics at Single-molecule Scales in Drosophila
Published on: September 8, 2023
Expression profiling of FSHD-1 and FSHD-2 cells during myogenic differentiation evidences common and distinctive gene
Stefania Cheli1, Stephanie François, Beatrice Bodega
1Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy.
Background:
Determine global gene dysregulation affecting 4q-linked (FSHD-1) and non 4q-linked (FSHD-2) cells during early stages of myogenic differentiation. This approach has been never applied to FSHD pathogenesis.
Methodology/Principal Findings:
By in vitro differentiation of FSHD-1 and FSHD-2 myoblasts and gene chip analysis we derived that gene expression profile is altered only in FSHD-1 myoblasts and FSHD-2 myotubes. The changes seen in FSHD-1 regarded a general defect in cell cycle progression, probably due to the upregulation of myogenic markers PAX3 and MYOD1, and a deficit of factors (SUV39H1 and HMGB2) involved in D4Z4 chromatin conformation. On the other hand, FSHD-2 mytubes were characterized by a general defect in RNA metabolism, protein synthesis and degradation and, to a lesser extent, in cell cycle. Common dysregulations regarded genes involved in response to oxidative stress and in sterol biosynthetic process. Interestingly, our results also suggest that miRNAs might be implied in both FSHD-1 and FSHD-2 gene dysregulation. Finally, in both cell differentiation systems, we did not observe a gradient of altered gene expression throughout the 4q35 chromosome.
Conclusions/Significance:
FSHD-1 and FSHD-2 cells showed, in different steps of myogenic differentiation, a global deregulation of gene expression rather than an alteration of expression of 4q35 specific genes. In general, FSHD-1 and FSHD-2 global gene deregulation interested common and distinctive biological processes. In this regard, defects of cell cycle progression (FSHD-1 and to a lesser extent FSHD-2), protein synthesis and degradation (FSHD-2), response to oxidative stress (FSHD-1 and FSHD-2), and cholesterol homeostasis (FSHD-1 and FSHD-2) may in general impair a correct myogenesis. Taken together our results recapitulate previously reported defects of FSHD-1, and add new insights into the gene deregulation characterizing both FSHD-1 and FSHD-2, in which miRNAs may play a role.
Insights
Facioscapulohumeral muscular dystrophy (FSHD) involves global gene dysregulation in both FSHD-1 and FSHD-2 cells during muscle development. These changes impact cell cycle, RNA metabolism, and oxidative stress, suggesting broader cellular defects beyond specific gene alterations.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder affecting muscle. It is classified into FSHD-1 (4q-linked) and FSHD-2 (non-4q-linked) forms.
- Early-stage myogenic differentiation is crucial for muscle development and function, and its disruption is implicated in FSHD pathogenesis.
Purpose of the Study:
- To investigate global gene expression profiles in early differentiating FSHD-1 and FSHD-2 cells.
- To identify specific molecular pathways and biological processes affected by gene dysregulation in FSHD subtypes.
Main Methods:
- In vitro differentiation of FSHD-1 and FSHD-2 myoblasts.
- Gene chip analysis to assess global gene expression profiles.
- Comparative analysis of gene expression between FSHD subtypes and controls.
Main Results:
- Gene expression profiles were altered in FSHD-1 myoblasts and FSHD-2 myotubes, but not uniformly across the 4q35 chromosome.
- FSHD-1 showed cell cycle defects linked to myogenic markers and chromatin factors, while FSHD-2 exhibited RNA metabolism and protein synthesis/degradation issues.
- Common dysregulations in both subtypes involved oxidative stress response and sterol biosynthesis; microRNAs (miRNAs) may contribute to gene deregulation.
Conclusions:
- FSHD-1 and FSHD-2 cells display distinct yet overlapping global gene deregulation patterns during myogenesis.
- These widespread gene expression changes, affecting critical cellular processes, contribute to impaired muscle development in FSHD.
- The findings highlight the complex genetic underpinnings of FSHD and suggest potential roles for miRNAs in disease mechanisms.
