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The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function

It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which t...

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Autores principales: Lorenzo-Martín, L. Francisco, Menacho-Márquez, Mauricio, Fernández-Parejo, Natalia, Rodríguez-Fdez, Sonia, Pascual, Gloria, Abad, Antonio, Crespo, Piero, Dosil, Mercedes, Benitah, Salvador A., Bustelo, Xosé R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187518/
https://www.ncbi.nlm.nih.gov/pubmed/35534539
http://dx.doi.org/10.1038/s41388-022-02341-7
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author Lorenzo-Martín, L. Francisco
Menacho-Márquez, Mauricio
Fernández-Parejo, Natalia
Rodríguez-Fdez, Sonia
Pascual, Gloria
Abad, Antonio
Crespo, Piero
Dosil, Mercedes
Benitah, Salvador A.
Bustelo, Xosé R.
author_facet Lorenzo-Martín, L. Francisco
Menacho-Márquez, Mauricio
Fernández-Parejo, Natalia
Rodríguez-Fdez, Sonia
Pascual, Gloria
Abad, Antonio
Crespo, Piero
Dosil, Mercedes
Benitah, Salvador A.
Bustelo, Xosé R.
author_sort Lorenzo-Martín, L. Francisco
collection PubMed
description It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which the activity of guanosine nucleotide exchange factors of the Vav subfamily has been manipulated using both gain- and loss-of-function strategies. These experiments indicate that Vav2 and Vav3 regulate the number, functional status, and responsiveness of hair follicle bulge stem cells. This is linked to gene expression programs related to the reinforcement of the identity and the quiescent state of normal SSCs. By contrast, in the case of cancer stem cells, they promote transcriptomal programs associated with the identity, activation state, and cytoskeletal remodeling. These results underscore the role of these Rho exchange factors in the regulation of normal and tumor epidermal stem cells.
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spelling pubmed-91875182022-06-12 The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function Lorenzo-Martín, L. Francisco Menacho-Márquez, Mauricio Fernández-Parejo, Natalia Rodríguez-Fdez, Sonia Pascual, Gloria Abad, Antonio Crespo, Piero Dosil, Mercedes Benitah, Salvador A. Bustelo, Xosé R. Oncogene Article It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which the activity of guanosine nucleotide exchange factors of the Vav subfamily has been manipulated using both gain- and loss-of-function strategies. These experiments indicate that Vav2 and Vav3 regulate the number, functional status, and responsiveness of hair follicle bulge stem cells. This is linked to gene expression programs related to the reinforcement of the identity and the quiescent state of normal SSCs. By contrast, in the case of cancer stem cells, they promote transcriptomal programs associated with the identity, activation state, and cytoskeletal remodeling. These results underscore the role of these Rho exchange factors in the regulation of normal and tumor epidermal stem cells. Nature Publishing Group UK 2022-05-09 2022 /pmc/articles/PMC9187518/ /pubmed/35534539 http://dx.doi.org/10.1038/s41388-022-02341-7 Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lorenzo-Martín, L. Francisco
Menacho-Márquez, Mauricio
Fernández-Parejo, Natalia
Rodríguez-Fdez, Sonia
Pascual, Gloria
Abad, Antonio
Crespo, Piero
Dosil, Mercedes
Benitah, Salvador A.
Bustelo, Xosé R.
The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function
title The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function
title_full The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function
title_fullStr The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function
title_full_unstemmed The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function
title_short The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function
title_sort rho guanosine nucleotide exchange factors vav2 and vav3 modulate epidermal stem cell function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187518/
https://www.ncbi.nlm.nih.gov/pubmed/35534539
http://dx.doi.org/10.1038/s41388-022-02341-7
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