Assay of Genome-Wide Transcriptome and Secreted Proteins on the Same Single Immune Cells by Microfluidics and RNA Sequencing

Given vast heterogeneity of immune cells, searching for gene expression and transcriptional networks belonging to specific cellular functions such as cytokine production has been challenging. To overcome this limitation, we developed a splittable single-cell microchip that integrates a high-density antibody array for cytokine protein detection, while the same single cells with protein profiles can be subsequently sequenced to obtain the genome-wide transcriptome. Combined with bioinformatics algorithms, we discovered a subgroup of highly coexpressed genes correlating with TNFα secretion in mouse macrophage cells. This technology and the data analysis may lead to an unprecedented understanding of regulation mechanisms of the immune system and have the potential to impact disease treatment and drug discovery.