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

Nature Communications
William StephensonRahul Satija

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.

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Methods Mentioned

BETA
Drop-seq
RNA-seq
scRNA-seq
chip
chips
flow-cytometry
PCR
PCA
FACS
Flow Cytometry

Software Mentioned

R
seq tools
Drop
seq
tSNE
scde
Seurat
Metafluidics

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