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 language | English |
|---|---|
| Pages (from-to) | 2278-2291 |
| Number of pages | 14 |
| Journal | Journal of the American Society of Nephrology : JASN |
| Volume | 31 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2020 |
Bibliographical note
Funding Information:T. Kalisky reports grants from the Israel Cancer Research Fund (ICRF), grants from The Israel Ministry of Science, and other funds from TaGeza Biopharmaceuticals (for consulting services provided), outside the submitted work. T. Kalisky has a patent application #US-20100255471, “Single cell gene expression for diagnosis, prognosis and identification of drug targets,” with Michael F. Clarke, Stephen R. Quake, Piero D. Dalerba, Huiping Liu, Anne A. Leyrat, and Maximilian Diehn with royalties paid to Stanford University; and a patent application #US-20130225435, “Methods and systems for analysis of single cells,” with Michael F. Clarke, Stephen R. Quake, Piero D. Dalerba, Huiping Liu, Anne A. Leyrat, Maximilian Diehn, Michael Rothenberg, Jianbin Wang, and Neethan Lobo with royalties paid to Stanford University. All remaining authors have nothing to disclose.
Funding Information:
Y. Wineberg, T.H. Bar-Lev, N. Ben-Haim, S. Oriel, E. Bucris, Y. Yehuda, and T. Kalisky were supported by the Israel Science Foundation (Israeli Center of Research Excellence [I-CORE] no. 1902/12 and grants 1634/13 and 2017/13), the Israel Cancer Association (grant 20150911), the Israel Ministry of Health (grant 3-10146), and the European Union’s Seventh Framework Programme (Marie Curie International Reintegration grant 618592). N. Pode-Shakked and B. Dekel were supported by the Israel Science Foundation (grants 2071/17 and 910/11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
Y. Wineberg, T.H. Bar-Lev, N. Ben-Haim, S. Oriel, E. Bucris, Y. Yehuda, and T. Kalisky were supported by the Israel Science Foundation (Israeli Center of Research Excellence [I-CORE] no. 1902/12 and grants 1634/13 and 2017/13), the Israel Cancer Association (grant 20150911), the Israel Ministry of Health (grant 3-10146), and the European Union's Seventh Framework Programme (Marie Curie International Reintegration grant 618592). N. Pode-Shakked and B. Dekel were supported by the Israel Science Foundation (grants 2071/17 and 910/11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
Copyright © 2020 by the American Society of Nephrology