Insights Gained and Future Outlook From scRNAseq Studies in Autoimmune Rheumatic Diseases

Autoimmune rheumatic diseases have a major impact on public health as one of the most common morbidities, and many of these disorders involve both local and systemic manifestations with severe consequences for patient health and quality of life. However, treatment options for many of these diseases remain inadequate for a substantial portion of patients, and progress in developing novel therapeutics has been slow. This lack of progress can be largely attributed to an insufficient understanding of the complex mechanisms driving pathogenesis. Recently, the emergence of single-cell RNA sequencing (scRNAseq) has offered a powerful new tool for interrogating rheumatic diseases, with the potential to assess biological heterogeneity and individual cell function in rheumatic diseases. In this review, we discuss the major insights gained from current scRNAseq interrogations of human rheumatic diseases. We highlight novel cell populations and key molecular signatures uncovered, and also raise a number of hypotheses for follow-up study that may be of interest to the field. We also provide an outlook into two emerging single-cell technologies (repertoire sequencing and spatial transcriptomics) that have yet to be utilized in the field of rheumatic diseases, but which offer immense potential in expanding our understanding of immune and stromal cell behavior. We hope that scRNAseq may serve as a wellspring for the generation and interrogation of novel hypotheses regarding autoreactive lymphocytes and tissue infiltration patterns, and help uncover novel avenues for therapeutic development.