Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation

William Stephenson, Laura T. Donlin, Andrew Butler, Cristina Rozo, Bernadette Bracken, Ali Rashidfarrokhi, Susan M. Goodman, Lionel B. Ivashkiv, Vivian P. Bykerk, Dana E. Orange, Robert B. Darnell, Harold P. Swerdlow, Rahul Satija

Research output: Contribution to journalArticle

Abstract

Droplet-based single-cell RNA-seq has emerged as a powerful technique for massively parallel cellular profiling. While this approach offers the exciting promise to deconvolute cellular heterogeneity in diseased tissues, the lack of cost-effective and user-friendly instrumentation has hindered widespread adoption of droplet microfluidic techniques. To address this, we developed a 3D-printed, low-cost droplet microfluidic control instrument and deploy it in a clinical environment to perform single-cell transcriptome profiling of disaggregated synovial tissue from five rheumatoid arthritis patients. We sequence 20,387 single cells revealing 13 transcriptomically distinct clusters. These encompass an unsupervised draft atlas of the autoimmune infiltrate that contribute to disease biology. Additionally, we identify previously uncharacterized fibroblast subpopulations and discern their spatial location within the synovium. We envision that this instrument will have broad utility in both research and clinical settings, enabling low-cost and routine application of microfluidic techniques.

Original languageEnglish (US)
Article number791
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Stephenson, W., Donlin, L. T., Butler, A., Rozo, C., Bracken, B., Rashidfarrokhi, A., Goodman, S. M., Ivashkiv, L. B., Bykerk, V. P., Orange, D. E., Darnell, R. B., Swerdlow, H. P., & Satija, R. (2018). Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation. Nature communications, 9(1), [791]. https://doi.org/10.1038/s41467-017-02659-x