A trans-eQTL network regulates osteoclast multinucleation and bone mass
| العنوان: | A trans-eQTL network regulates osteoclast multinucleation and bone mass |
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| المؤلفون: | Jacques Behmoaras, Marie Pereira, Enrico Petretto, Peter I. Croucher, Amelia Li Min Tan, Kwon-Sik Park, Graham R. Williams, J. H. Duncan Bassett, Maxime Rotival, Jeong-Hun Ko, Hayley Protheroe, Kee-Beom Kim, John G. Logan |
| المساهمون: | Imperial College London, Hammersmith Hospital NHS Imperial College Healthcare, University of Virginia, Duke-NUS Medical School [Singapore], University of New South Wales [Sydney] (UNSW), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Medical Research Council ‘Control of Macrophage Multinucleation in Health and Disease’ (MR/N01121X/1 to JB, GRW, JHDB), a Wellcome Trust Strategic Award (Grant Number 101123 to GRW and JHDB) and National Institutes of Health/ National Cancer Institute (NIH/NCI U01CA224293)., Medical Research Council (MRC) |
| المصدر: | eLife eLife, 2020, 9, pp.e55549. ⟨10.7554/eLife.55549⟩ eLife, Vol 9 (2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Life Sciences & Biomedicine - Other Topics, Male, Network - organization, Rat and human model, Gene regulatory network, Cell biology and structure, Osteoclasts, Genome-wide association study, DETERMINANTS, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 0601 Biochemistry and Cell Biology, Rats, Inbred WKY, bone, Mice, 0302 clinical medicine, Bone Density, genetics, Gene Regulatory Networks, rat, Biology (General), MACROPHAGES, Genomics and evolution, RISK, Mice, Knockout, General Neuroscience, General Medicine, Phenotype, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Knockout mouse, osteoclast, Genetics Humans, Medicine, PHOSPHATIDYLINOSITOL 3-KINASE, Bone Biology, Female, Human - human interaction, Life Sciences & Biomedicine, Research Article, Human, Osteoclast gene, QH301-705.5, Science, Quantitative Trait Loci, Quantitative trait locus, Biology, General Biochemistry, Genetics and Molecular Biology, Bone resorption, 03 medical and health sciences, Osteoclast, medicine, genomics, Animals, GENOME-WIDE ASSOCIATION, DC-STAMP, Bone Resorption, Gene, METAANALYSIS, mouse, Science & Technology, General Immunology and Microbiology, COMPLEX TRAITS, Genetics and Genomics, Cell Biology, Rats, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Rats, Inbred Lew, network, SYSTEMS GENETICS, MINERAL DENSITY, Genome-Wide Association Study |
| الوصف: | International audience; Functional characterisation of cell-type-specific regulatory networks is key to establish a causal link between genetic variation and phenotype. The osteoclast offers a unique model for interrogating the contribution of co-regulated genes to in vivo phenotype as its multinucleation and resorption activities determine quantifiable skeletal traits. Here we took advantage of a trans-regulated gene network (MMnet, macrophage multinucleation network) which we found to be significantly enriched for GWAS variants associated with bone-related phenotypes. We found that the network hub gene Bcat1 and seven other co-regulated MMnet genes out of 13, regulate bone function. Specifically, global (Pik3cb-/-, Atp8b2+/-, Igsf8-/-, Eml1-/-, Appl2-/-, Deptor-/-) and myeloid-specific Slc40a1 knockout mice displayed abnormal bone phenotypes. We report opposing effects of MMnet genes on bone mass in mice and osteoclast multinucleation/resorption in humans with strong correlation between the two. These results identify MMnet as a functionally conserved network that regulates osteoclast multinucleation and bone mass. |
| تدمد: | 2050-084X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::493a34e7e75296bafede564fed28020aTest https://pubmed.ncbi.nlm.nih.gov/32553114Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....493a34e7e75296bafede564fed28020a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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