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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, View ORCID ProfileTomer Kalisky
doi: https://doi.org/10.1101/688564
Yishay Wineberg
1Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900
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Tali Hana Bar-Lev
1Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900
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Anna Futorian
2The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 52900
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Nissim Ben-Haim
1Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900
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Leah Armon
2The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 52900
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Debby Ickowicz
2The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 52900
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Sarit Oriel
1Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900
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Efrat Bucris
1Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900
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Yishai Yehuda
1Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900
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Naomi Pode-Shakked
4Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Israel 52621
5Division of Pediatric Nephrology, Sheba Medical Center, Tel-Hashomer, Israel 52621
6Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Shlomit Gilad
3The Nancy and Stephen Grand Israel National Center for Personalized Medicine (G-INCPM), Weizmann Institute of Science, Rehovot, Israel 7610001
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Sima Benjamin
3The Nancy and Stephen Grand Israel National Center for Personalized Medicine (G-INCPM), Weizmann Institute of Science, Rehovot, Israel 7610001
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Peter Hohenstein
7Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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Benjamin Dekel
4Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Israel 52621
5Division of Pediatric Nephrology, Sheba Medical Center, Tel-Hashomer, Israel 52621
6Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Achia Urbach
2The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 52900
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Tomer Kalisky
1Department of Bioengineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel 52900
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  • ORCID record for Tomer Kalisky
  • For correspondence: tomer.kalisky@gmail.com
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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.

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  • ↵* Co-first authors

  • ↵** Co-senior authors

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Posted July 01, 2019.
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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
bioRxiv 688564; doi: https://doi.org/10.1101/688564
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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
bioRxiv 688564; doi: https://doi.org/10.1101/688564

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