Correlation of Gene Expression and Genome Mutation in Single B-Cells

Abstract

High-throughput measurement of gene-expression and immune receptor repertoires have recently become powerful tools in the study of adaptive immune response. However, despite their now-widespread use, both tend to discard cell identity by treating cell populations in bulk, and therefore lose the correlation between genetic variability and gene-expression at the single cell level. In order to recover this information, we developed a method to simultaneously measure gene expression profiles and genome mutations in single cells. We applied this method by quantifying the relationships between gene expression and antibody mutation in ensembles of individual B-cells from immunized mice. The results reveal correlations reflecting the manner in which information propagates between a B-cell's antigen receptors, its gene expression, and its mutagenic machinery, and demonstrate the power of this approach to illuminate both heterogeneity and physiology in cell populations. © 2013 Weinstein et al.