Report: Mapping FSHD through single nuclei RNA sequencing

Posted by Friends of FSH Research on Jan 30, 2026

Report by Dr. Tasca
See also Mapping Facioscapulohumeral muscular dystrophy through single nuclei RNA sequencing

This project used a cutting-edge genetic technique, called single-nucleus RNA sequencing, to study how facioscapulohumeral muscular dystrophy (FSHD) affects individual cells within muscle biopsies.  We analysed muscle samples from people with FSHD at different stages of disease activity, as well as from healthy volunteers.

We confirmed that areas of muscle that appear “active” on MRI (STIR-positive regions) show strong signs of inflammation, immune system activation, and tissue stress, while “inactive” regions are much closer to healthy muscle at the molecular level.  In active FSHD muscle, we saw more immune cells (such as macrophages and T cells), more supporting stromal cells, and fewer normal muscle fibres, suggesting ongoing damage and tissue remodelling.  We also found that muscle stem cells (satellite cells) and fibro-adipogenic progenitors (cells that help organise the tissue environment) appear to be abnormally activated and may not complete normal repair, which could contribute to poor regeneration over time.

By following some patients over two years, we observed that the biggest molecular changes in diseased muscle accumulate more slowly and are most evident at later time points, supporting the idea that FSHD progression involves gradual, long-term remodelling of the muscle environment.  Together, these findings provide a detailed map of how different cell types behave in FSHD muscle and highlight potential cellular and molecular targets for future therapies aimed at reducing inflammation, protecting muscle fibres, and improving regeneration.