Generating a 10 million cell atlas of immune responses to cytokine stimulation using high throughput single cell RNA sequencing 3845

Abstract Description Cytokines are produced by immune cells to achieve immunological threat clearance and maintain homeostasis. Understanding their role in shaping immune responses can help drive the development of new immunotherapies. To date there are no studies that have comprehensively characterized the impact of each cytokine on human PBMCs as it entails in depth characterization of thousands of unique cytokine – immune cell interactions. Single cell RNA sequencing (scRNA-seq) is a powerful tool for characterizing the transcriptional heterogeneity of cells in a variety of biological systems and research applications. Currently many single cell technologies assay a limited number of cells and samples in a single experiment. Here, we implemented workflow and reagent changes to the Evercode scRNA-seq combinatorial barcoding technology and profiled 10 million cells from 12 PBMC donors treated with 90 different cytokines. We identify 18 immune cell types and characterize a total of 19,440, donor-specific, cell type-cytokine interactions. Using this approach, we quantify the magnitude of each response by identifying the number of differentially expressed genes relative to control cells. Lastly, we show that each cytokine can induce both cell type-specific and broad gene expression changes. Overall, we anticipate this method will democratize multi-million single cell sequencing experiments and inspire researchers to scale their experiments to make significant advances in biological research. Topic Categories Cytokines and Chemokines and Their Receptors (CCR)