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A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver

Cells with slow proliferation kinetics that retain the nuclear label over long time periods–the label-retaining cells (LRCs)–represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in...

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Autores principales: Viil, Janeli, Klaas, Mariliis, Valter, Kadri, Belitškin, Denis, Ilmjärv, Sten, Jaks, Viljar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234023/
https://www.ncbi.nlm.nih.gov/pubmed/28084309
http://dx.doi.org/10.1038/srep40322
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author Viil, Janeli
Klaas, Mariliis
Valter, Kadri
Belitškin, Denis
Ilmjärv, Sten
Jaks, Viljar
author_facet Viil, Janeli
Klaas, Mariliis
Valter, Kadri
Belitškin, Denis
Ilmjärv, Sten
Jaks, Viljar
author_sort Viil, Janeli
collection PubMed
description Cells with slow proliferation kinetics that retain the nuclear label over long time periods–the label-retaining cells (LRCs)–represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in normal non-injured livers and characterized their regenerative properties in vivo and in culture. We found that LLRCs were located in biliary vessels and participated in the regeneration of biliary but not hepatocyte injury. In culture experiments the sorted LLRCs displayed an enhanced self-renewal capacity but a unipotent biliary differentiation potential. Transcriptome analysis revealed a unique set of tumorigenesis- and nervous system-related genes upregulated in LLRCs when compared to non-LRC cholangiocytes. We conclude that the LLRCs established during the normal morphogenesis of the liver do not represent a multipotent primitive somatic stem cell population but act as unipotent biliary progenitor cells.
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spelling pubmed-52340232017-01-18 A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver Viil, Janeli Klaas, Mariliis Valter, Kadri Belitškin, Denis Ilmjärv, Sten Jaks, Viljar Sci Rep Article Cells with slow proliferation kinetics that retain the nuclear label over long time periods–the label-retaining cells (LRCs)–represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in normal non-injured livers and characterized their regenerative properties in vivo and in culture. We found that LLRCs were located in biliary vessels and participated in the regeneration of biliary but not hepatocyte injury. In culture experiments the sorted LLRCs displayed an enhanced self-renewal capacity but a unipotent biliary differentiation potential. Transcriptome analysis revealed a unique set of tumorigenesis- and nervous system-related genes upregulated in LLRCs when compared to non-LRC cholangiocytes. We conclude that the LLRCs established during the normal morphogenesis of the liver do not represent a multipotent primitive somatic stem cell population but act as unipotent biliary progenitor cells. Nature Publishing Group 2017-01-13 /pmc/articles/PMC5234023/ /pubmed/28084309 http://dx.doi.org/10.1038/srep40322 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Viil, Janeli
Klaas, Mariliis
Valter, Kadri
Belitškin, Denis
Ilmjärv, Sten
Jaks, Viljar
A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver
title A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver
title_full A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver
title_fullStr A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver
title_full_unstemmed A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver
title_short A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver
title_sort label-retaining but unipotent cell population resides in biliary compartment of mammalian liver
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234023/
https://www.ncbi.nlm.nih.gov/pubmed/28084309
http://dx.doi.org/10.1038/srep40322
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