Annals of the Rheumatic Diseases · Oct 26, 2026

Medicalising the Human Cell Atlas for musculoskeletal disease: towards a translational roadmap

By Hourston GJM, To K, Teichmann SA et al.

The Human Cell Atlas (HCA) has fundamentally changed the way biologists describe human tissues. However, its greatest promise for musculoskeletal (MSK) practitioners lies ahead: to convert cellular maps into clinically actionable knowledge. MSK diseases are common, heterogeneous, and often insufficiently stratified by current diagnostic labels. The same label, such as rheumatoid arthritis, can conceal distinct cellular mechanisms, tissue niches, and therapeutic vulnerabilities. Conversely, apparently different disorders such as tendinopathy or fibrotic capsulitis can share convergent stromal, immune, vascular, or neuronal programmes. A MSK-HCA therefore should not be conceived as a passive reference catalogue. It should be 'medicalised': designed from the outset to connect tissue atlases with clinical phenotypes, imaging, biospecimens, genetic risk, biomarkers, perturbation experiments, and interventional trials. In this review, we describe how single-cell, single-nucleus, spatial, and multiomic approaches are beginning to map MSK tissues from development to ageing and from health to disease. We highlight examples in embryonic skeletal development, bone marrow, muscle ageing, osteoarthritis, rheumatoid arthritis, tendon disease, and inflammatory fibrosis and show how these data can reframe disease taxonomy around pathogenic cell states rather than organ-level labels alone. We propose a translational roadmap in which atlases define healthy reference coordinates, identify disease-enriched cell states, nominate biomarkers and therapeutic targets, and then learn from clinical trial outcomes. For clinicians, the MSK-HCA offers a route to mechanism-led diagnosis and patient stratification; for scientists, it provides a shared coordinate system for testing how genes, cells, and tissue microenvironments generate disease. Medicalising the HCA could make cellular medicine a practical foundation for precision rheumatology and regenerative MSK therapy.

doi.org/10.1016/j.ard.2026.09.023Open accessPubMed 42934004AI & data