Single-cell RNA sequencing reveals mRNA splice isoform switching during kidney development

Kidney development is a complex process involving multiple interacting and transforming cell types. These cell types were recently characterized using the Drop-seq single-cell technology for measuring gene expression from many thousands of individual cells. However, many genes can also be alternatively spliced and this creates an additional layer of cellular heterogeneity that cannot be measured with the Drop-seq technology. This study describes the use of full transcript length single-cell RNA sequencing to characterize alternative splicing in the developing mouse fetal kidney; in particular, the identification of genes that are alternatively spliced during the transition from mesenchymal to epithelial cell states, as well as their splicing regulators. These results improve our understanding of the molecular mechanisms involved in kidney development. Overall design: We performed single cell RNA sequencing on 576 individual cells from the kidneys of E18.5 mouse embryos using the Smartseq2 protocol for sequencing full transcript lengths