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RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression

Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found th...

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Autores principales: Casanova-Acebes, María, Menéndez-Gutiérrez, María Piedad, Porcuna, Jesús, Álvarez-Errico, Damiana, Lavin, Yonit, García, Ana, Kobayashi, Soma, Le Berichel, Jessica, Núñez, Vanessa, Were, Felipe, Jiménez-Carretero, Daniel, Sánchez-Cabo, Fátima, Merad, Miriam, Ricote, Mercedes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125161/
https://www.ncbi.nlm.nih.gov/pubmed/32246014
http://dx.doi.org/10.1038/s41467-020-15371-0
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author Casanova-Acebes, María
Menéndez-Gutiérrez, María Piedad
Porcuna, Jesús
Álvarez-Errico, Damiana
Lavin, Yonit
García, Ana
Kobayashi, Soma
Le Berichel, Jessica
Núñez, Vanessa
Were, Felipe
Jiménez-Carretero, Daniel
Sánchez-Cabo, Fátima
Merad, Miriam
Ricote, Mercedes
author_facet Casanova-Acebes, María
Menéndez-Gutiérrez, María Piedad
Porcuna, Jesús
Álvarez-Errico, Damiana
Lavin, Yonit
García, Ana
Kobayashi, Soma
Le Berichel, Jessica
Núñez, Vanessa
Were, Felipe
Jiménez-Carretero, Daniel
Sánchez-Cabo, Fátima
Merad, Miriam
Ricote, Mercedes
author_sort Casanova-Acebes, María
collection PubMed
description Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found that serous-cavity TRMs (LPMs) are highly enriched in RXR transcripts and RXR-response elements. Here, we show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. RXR deficiency impairs neonatal expansion of the LPM pool and reduces the survival of adult LPMs through excess lipid accumulation. We also find that peritoneal LPMs infiltrate early ovarian tumours and that RXR deletion diminishes LPM accumulation in tumours and strongly reduces ovarian tumour progression in mice. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes.
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spelling pubmed-71251612020-04-06 RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression Casanova-Acebes, María Menéndez-Gutiérrez, María Piedad Porcuna, Jesús Álvarez-Errico, Damiana Lavin, Yonit García, Ana Kobayashi, Soma Le Berichel, Jessica Núñez, Vanessa Were, Felipe Jiménez-Carretero, Daniel Sánchez-Cabo, Fátima Merad, Miriam Ricote, Mercedes Nat Commun Article Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found that serous-cavity TRMs (LPMs) are highly enriched in RXR transcripts and RXR-response elements. Here, we show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. RXR deficiency impairs neonatal expansion of the LPM pool and reduces the survival of adult LPMs through excess lipid accumulation. We also find that peritoneal LPMs infiltrate early ovarian tumours and that RXR deletion diminishes LPM accumulation in tumours and strongly reduces ovarian tumour progression in mice. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes. Nature Publishing Group UK 2020-04-03 /pmc/articles/PMC7125161/ /pubmed/32246014 http://dx.doi.org/10.1038/s41467-020-15371-0 Text en © The Author(s) 2020 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/.
spellingShingle Article
Casanova-Acebes, María
Menéndez-Gutiérrez, María Piedad
Porcuna, Jesús
Álvarez-Errico, Damiana
Lavin, Yonit
García, Ana
Kobayashi, Soma
Le Berichel, Jessica
Núñez, Vanessa
Were, Felipe
Jiménez-Carretero, Daniel
Sánchez-Cabo, Fátima
Merad, Miriam
Ricote, Mercedes
RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
title RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
title_full RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
title_fullStr RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
title_full_unstemmed RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
title_short RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
title_sort rxrs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125161/
https://www.ncbi.nlm.nih.gov/pubmed/32246014
http://dx.doi.org/10.1038/s41467-020-15371-0
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