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Profiling joint tissues at single-cell resolution: advances and insights

Nature Reviews Rheumatology volume 20, pages 7–20 (2024)Cite this article

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Abstract

Advances in the profiling of human joint tissues at single-cell resolution have provided unique insights into the organization and function of these tissues in health and disease. Data generated by various single-cell technologies, including single-cell RNA sequencing and cytometry by time-of-flight, have identified the distinct subpopulations that constitute these tissues. These timely studies have provided the building blocks for the construction of single-cell atlases of joint tissues including cartilage, bone and synovium, leading to the identification of developmental trajectories, deciphering of crosstalk between cells and discovery of rare populations such as stem and progenitor cells. In addition, these studies have revealed unique pathogenetic populations that are potential therapeutic targets. The use of these approaches in synovial tissues has helped to identify how distinct cell subpopulations can orchestrate disease initiation and progression and be responsible for distinct pathological outcomes. Additionally, repair of tissues such as cartilage and meniscus remains an unmet medical need, and single-cell methodologies can be invaluable in providing a blueprint for both effective tissue-engineering strategies and therapeutic interventions for chronic joint diseases such as osteoarthritis and rheumatoid arthritis.

Key points

  • Single-cell technologies (transcriptomic, proteomic and epigenomic) have seen considerable advancement in the past decade in elucidating the complexity and heterogeneity of cell populations that constitute joint tissues.

  • Studies using single-cell techniques have revealed the developmental trajectories of cell populations and their crosstalk.

  • Key cell populations with distinct pathogenetic or regenerative functions have been identified and can provide precise therapeutic targets for joint diseases.

  • Identification of pathogenetic cell populations provides insight into patient heterogeneity and cellular biomarkers for clinical stratification.

  • Single-cell data provide high-resolution snapshots of response to drugs in patient samples.

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Fig. 1: The major cell subpopulations identified in joint tissues.
Fig. 2: Patient stratification strategies based on single-cell ‘omics’ for a precision medicine framework.

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  1. Department of Orthopaedic Surgery, School of Medicine, Stanford University, Stanford, CA, USA

    Akshay Pandey & Nidhi Bhutani

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Pandey, A., Bhutani, N. Profiling joint tissues at single-cell resolution: advances and insights. Nat Rev Rheumatol 20, 7–20 (2024). https://doi.org/10.1038/s41584-023-01052-x

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