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

Abstract

During mammalian kidney development, nephron progenitors undergo a mesenchymal to epithelial transition and eventually differentiate into the various tubular segments of the nephron. Recently, the different cell types in the developing kidney were characterized using the Dropseq single cell RNA sequencing technology for measuring gene expression from thousands of individual cells. However, many genes can also be alternatively spliced and this creates an additional layer of heterogeneity. We therefore used full transcript length single-cell RNA sequencing to obtain the transcriptomes of 544 individual cells from mouse embryonic kidneys. We first used gene expression levels to identify each cell type. Then, we comprehensively characterized the splice isoform switching that occurs during the transition between mesenchymal and epithelial cellular states and identified several putative splicing regulators, including the genes Esrp1/2 and Rbfox1/2. We anticipate that these results will improve our understanding of the molecular mechanisms involved in kidney development.