Posted by Friends of FSH Research on Jun 23, 2026
Update by Dr. van der Maarel
See also Spatial Transcriptomics in FSHD Skeletal Muscle
FSHD is a muscle disease caused by the abnormal activation of a gene called DUX4, which is normally only active in early embryonic development. When DUX4 turns on in muscle cells, it triggers harmful processes that damage muscle tissue. Interestingly, in tissue culture only a very small number of muscle cell nuclei, sometimes as few as 1 in 200, are actively producing DUX4 at any given moment. How this translates to FSHD muscle and how such rare activity leads to severe muscle loss is still not fully understood. Studying this is difficult because DUX4 appears only briefly and in scattered spots, making it hard to detect and track.
Most past studies looked at cells in isolation and lost information about where things were happening in the tissue. However, this spatial context is crucial to understanding how the disease develops. In this project, we use a newer method called spatial transcriptomics, which allows us to study gene activity while preserving the exact location within muscle tissue. So far, we have identified small, localized regions where DUX4 and its target genes are active, and we see that damage patterns vary widely across different areas of the muscle. We are now analyzing the surrounding tissue in more detail to understand how DUX4 affects nearby cells and contributes to muscle damage. We are also combining this with other techniques to study individual muscle fibers, helping us confirm and better understand how uneven and sporadic DUX4 activity is within muscle. Together, these approaches are giving us a clearer picture of how DUX4 drives FSHD at both the molecular and tissue level.
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