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

Yishay Wineberg, Tali Hana Bar-Lev, Anna Futorian, Nissim Ben-Haim, Leah Armon, Debby Ickowicz, Sarit Oriel, Efrat Bucris, Yishai Yehuda, Naomi Pode-Shakked, Shlomit Gilad, Sima Benjamin, Peter Hohenstein, Benjamin Dekel, Achia Urbach, Tomer Kalisky

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background During mammalian kidney development, nephron progenitors undergo a mesenchymal-to-epithelial transition and eventually differentiate into the various tubular segments of the nephron. Recently, Drop-seq single-cell RNA sequencing technology for measuring gene expression from thousands of individual cells identified the different cell types in the developing kidney. However, that analysis did not include the additional layer of heterogeneity that alternative mRNA splicing creates. Methods Full transcript length single-cell RNA sequencing characterized the transcriptomes of 544 individual cells from mouse embryonic kidneys. Results Gene expression levels measured with full transcript length single-cell RNA sequencing identified each cell type. Further analysis comprehensively characterized splice isoform switching during the transition between mesenchymal and epithelial cellular states, which is a key transitional process in kidney development. The study also identified several putative splicing regulators, including the genes Esrp1/2 and Rbfox1/2. Conclusions Discovery of the sets of genes that are alternatively spliced as the fetal kidney mesenchyme differentiates into tubular epithelium will improve our understanding of the molecular mechanisms that drive kidney development.

Original languageEnglish
Pages (from-to)2278-2291
Number of pages14
JournalJournal of the American Society of Nephrology : JASN
Volume31
Issue number10
DOIs
StatePublished - Oct 2020

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Copyright © 2020 by the American Society of Nephrology

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