RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
| Autor: | Vanessa Núñez, Damiana Álvarez-Errico, Jesús Porcuna, Felipe Were, Fátima Sánchez-Cabo, Maria Casanova-Acebes, Yonit Lavin, María P. Menéndez-Gutiérrez, Daniel Jimenez-Carretero, Soma Kobayashi, Ana Belén García, Jessica Le Berichel, Mercedes Ricote, Miriam Merad |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), Fundación La Marató TV3, Comunidad de Madrid (España), Fundación ProCNIC |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Science General Physics and Astronomy Retinoid X receptor Biology Hormone receptors General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Peritoneal macrophages Mice 0302 clinical medicine Ovarian cancer medicine Transcriptional regulation Macrophage Animals lcsh:Science Transcriptomics Regulation of gene expression Ovarian Neoplasms Multidisciplinary Gene Expression Profiling General Chemistry medicine.disease Chromatin Mice Inbred C57BL Serous fluid 030104 developmental biology Retinoid X Receptors Animals Newborn Gene Expression Regulation 030220 oncology & carcinogenesis Cancer research Disease Progression Macrophages Peritoneal lipids (amino acids peptides and proteins) lcsh:Q Female Signal transduction Signal Transduction |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) |
| Popis: | 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. Macrophages can differentiate to perform homeostatic tissue-specific functions. Here the authors show that RXR signalling is critical for large peritoneal macrophage (LPM) expansion during neonatal life and LPM lipid metabolism and survival during adult homeostasis, and that ovarian cancer growth relies on RXR-dependent LPMs. |
| Databáze: | OpenAIRE |
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