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Direct Isolation and Characterization of Human Nephron Progenitors

Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NP...

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Autores principales: Da Sacco, Stefano, Thornton, Matthew E., Petrosyan, Astgik, Lavarreda‐Pearce, Maria, Sedrakyan, Sargis, Grubbs, Brendan H., De Filippo, Roger E., Perin, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442819/
https://www.ncbi.nlm.nih.gov/pubmed/28191781
http://dx.doi.org/10.5966/sctm.2015-0429
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author Da Sacco, Stefano
Thornton, Matthew E.
Petrosyan, Astgik
Lavarreda‐Pearce, Maria
Sedrakyan, Sargis
Grubbs, Brendan H.
De Filippo, Roger E.
Perin, Laura
author_facet Da Sacco, Stefano
Thornton, Matthew E.
Petrosyan, Astgik
Lavarreda‐Pearce, Maria
Sedrakyan, Sargis
Grubbs, Brendan H.
De Filippo, Roger E.
Perin, Laura
author_sort Da Sacco, Stefano
collection PubMed
description Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NPs, but very little is known about this population in humans, since it is exhausted before birth and strategies for its direct isolation are still limited. Here we report an efficient protocol for direct isolation of human NPs without genetic manipulation or stepwise induction procedures. With the use of RNA‐labeling probes, we isolated SIX2(+)CITED1(+) cells from human fetal kidney for the first time. We confirmed their nephrogenic state by gene profiling and evaluated their nephrogenic capabilities in giving rise to mature renal cells. We also evaluated the ability to culture these cells without complete loss of SIX2 and CITED1 expression over time. In addition to defining the gene profile of human NPs, this in vitro system facilitates studies of human renal development and provides a novel tool for renal regeneration and bioengineering purposes. Stem Cells Translational Medicine 2017;6:419–433
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spelling pubmed-54428192017-06-15 Direct Isolation and Characterization of Human Nephron Progenitors Da Sacco, Stefano Thornton, Matthew E. Petrosyan, Astgik Lavarreda‐Pearce, Maria Sedrakyan, Sargis Grubbs, Brendan H. De Filippo, Roger E. Perin, Laura Stem Cells Transl Med Translational Research Articles and Reviews Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NPs, but very little is known about this population in humans, since it is exhausted before birth and strategies for its direct isolation are still limited. Here we report an efficient protocol for direct isolation of human NPs without genetic manipulation or stepwise induction procedures. With the use of RNA‐labeling probes, we isolated SIX2(+)CITED1(+) cells from human fetal kidney for the first time. We confirmed their nephrogenic state by gene profiling and evaluated their nephrogenic capabilities in giving rise to mature renal cells. We also evaluated the ability to culture these cells without complete loss of SIX2 and CITED1 expression over time. In addition to defining the gene profile of human NPs, this in vitro system facilitates studies of human renal development and provides a novel tool for renal regeneration and bioengineering purposes. Stem Cells Translational Medicine 2017;6:419–433 John Wiley and Sons Inc. 2016-09-09 2017-02 /pmc/articles/PMC5442819/ /pubmed/28191781 http://dx.doi.org/10.5966/sctm.2015-0429 Text en © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Translational Research Articles and Reviews
Da Sacco, Stefano
Thornton, Matthew E.
Petrosyan, Astgik
Lavarreda‐Pearce, Maria
Sedrakyan, Sargis
Grubbs, Brendan H.
De Filippo, Roger E.
Perin, Laura
Direct Isolation and Characterization of Human Nephron Progenitors
title Direct Isolation and Characterization of Human Nephron Progenitors
title_full Direct Isolation and Characterization of Human Nephron Progenitors
title_fullStr Direct Isolation and Characterization of Human Nephron Progenitors
title_full_unstemmed Direct Isolation and Characterization of Human Nephron Progenitors
title_short Direct Isolation and Characterization of Human Nephron Progenitors
title_sort direct isolation and characterization of human nephron progenitors
topic Translational Research Articles and Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442819/
https://www.ncbi.nlm.nih.gov/pubmed/28191781
http://dx.doi.org/10.5966/sctm.2015-0429
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