High-throughput single cell gene expression profiling of peripheral blood mononuclear cells from healthy donor and individuals with rheumatoid arthritis

Abstract Peripheral blood has been extensively studied using gene expression microarrays in the past. These studies have revealed numerous genes that are differentially expressed between diseased and healthy populations. However, almost all these studies utilized bulk RNA isolated from blood cells for analysis, therefore masking the contribution from different types of cells in the sample. Here, we demonstrated the use of high throughput single cell gene expression analysis to profile peripheral blood mononuclear cells. Using BDTM Resolve and next-gen sequencing, we studied the single cell profiles of a total of ~27,000 cells obtained from two individuals with rheumatoid arthritis (RA) and a healthy donor. By studying either the profiles of the entire transcriptome or a representative set of ~500 gene markers via targeted amplification, we were able to observe distinct expression patterns in the monocyte population in RA patients as compared to controls, as well as difference in overall population architecture. At similar or even lower sequencing cost per cell, targeted amplification of representative gene markers offers much higher resolution of gene expression analysis of highly similar subtypes of cells (such as T cells) as compared to the whole transcriptome approach. These results demonstrated that high-resolution single-cell gene expression analysis using targeted amplification can potentially be used to routinely examine peripheral blood cells in various conditions, and may serve as new screening or diagnostic approach.