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Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis

The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only...

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Autores principales: Bais, Abha S., Cerqueira, Débora M., Clugston, Andrew, Bodnar, Andrew J., Ho, Jacqueline, Kostka, Dennis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599654/
https://www.ncbi.nlm.nih.gov/pubmed/34789782
http://dx.doi.org/10.1038/s41598-021-01790-6
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author Bais, Abha S.
Cerqueira, Débora M.
Clugston, Andrew
Bodnar, Andrew J.
Ho, Jacqueline
Kostka, Dennis
author_facet Bais, Abha S.
Cerqueira, Débora M.
Clugston, Andrew
Bodnar, Andrew J.
Ho, Jacqueline
Kostka, Dennis
author_sort Bais, Abha S.
collection PubMed
description The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single-cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle-related genes Birc5, Cdca3, Smc2 and Smc4 in “primed” nephron progenitors. In addition, augmented expression of cell cycle related genes Birc5, Cks2, Ccnb1, Ccnd1 and Tuba1a/b was detected in immature distal tubules, suggesting cell cycle regulation may be required for early events of nephron patterning and tubular fusion between the distal nephron and collecting duct epithelia.
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spelling pubmed-85996542021-11-19 Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis Bais, Abha S. Cerqueira, Débora M. Clugston, Andrew Bodnar, Andrew J. Ho, Jacqueline Kostka, Dennis Sci Rep Article The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single-cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle-related genes Birc5, Cdca3, Smc2 and Smc4 in “primed” nephron progenitors. In addition, augmented expression of cell cycle related genes Birc5, Cks2, Ccnb1, Ccnd1 and Tuba1a/b was detected in immature distal tubules, suggesting cell cycle regulation may be required for early events of nephron patterning and tubular fusion between the distal nephron and collecting duct epithelia. Nature Publishing Group UK 2021-11-17 /pmc/articles/PMC8599654/ /pubmed/34789782 http://dx.doi.org/10.1038/s41598-021-01790-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bais, Abha S.
Cerqueira, Débora M.
Clugston, Andrew
Bodnar, Andrew J.
Ho, Jacqueline
Kostka, Dennis
Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
title Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
title_full Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
title_fullStr Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
title_full_unstemmed Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
title_short Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
title_sort single-cell rna sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599654/
https://www.ncbi.nlm.nih.gov/pubmed/34789782
http://dx.doi.org/10.1038/s41598-021-01790-6
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