Abstract

Linking Genes to Function for Thousands of Single Cells Using Nanovial Technology

Dino Di Carlo, Armond and Elena Hairapetian Chair in Engineering and Medicine, Professor and Vice Chair of Bioengineering, University of California Los Angeles

We have developed 3D-shaped hydrogel microparticle platforms to capture cells, as well as isolate and label their secretions. These “lab on a particle” systems enable sorting cells based on secreted products for the discovery of antibodies, the development of cell lines producing recombinant products, and the selection of functional cells for cell therapies. Each cell and its secreted products can be analyzed using widely available flow cytometers and single-cell sequencing instruments, promising to democratize single-cell technologies. I will discuss our latest results linking the transcriptomes of single cells to the secreted products they produce. I will cover two example applications of this secretion encoded single-cell sequencing (SEC-seq) workflow. In a first example we uncover gene networks associated with high secretion of immunoglobulin G in human plasma cells, one of the most highly secreting cell types in the body. In a second application we characterize a unique transcriptionally-defined cluster of mesenchymal stromal cells (MSCs) that secrete higher levels of vascular endothelial growth factor (VEGF). VEGF is a pro-regenerative growth factor that is thought to drive therapeutic benefit in MSC-based therapeutics. I will summarize the potential for nanovial technology to promote understanding and engineering of functional properties in single cells, and ultimately drive the next-generation of cell therapies.