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Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-17 (2019), Nature Communications, 10. NATURE PUBLISHING GROUP, Nature Communications, Rojo, R, Raper, A, Ozdemir, D D, Lefevre, L, Grabert, K, Wollscheid-Lengeling, E, Bradford, B, Caruso, M, Gazova, I, Sanchez, A, Lisowski, Z M, Alves, J, Molina-Gonzalez, I, Davtyan, H, Lodge, R J, Glover, J D, Wallace, R, Munro, D A D, David, E, Amit, I, Miron, V E, Priller, J, Jenkins, S J, Hardingham, G E, Blurton-Jones, M, Mabbott, N A, Summers, K M, Hohenstein, P, Hume, D A & Pridans, C 2019, ' Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. ', Nature Communications, vol. 10, 3215 . https://doi.org/10.1038/s41467-019-11053-8
- Publication Year :
- 2019
-
Abstract
- The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1rΔFIRE/ΔFIRE mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1rΔFIRE/ΔFIRE mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r−/− rodents. Csf1rΔFIRE/ΔFIRE mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.<br />The lineage-specific receptor CSF1R controls macrophage development and homeostasis. Here the authors show that deletion of a conserved Csf1r enhancer (FIRE) selectively depletes brain microglia and resident macrophages in the epidermis, kidney, heart and peritoneum of otherwise healthy mice.
- Subjects :
- 0301 basic medicine
Male
Cellular differentiation
Neuroimmunology
General Physics and Astronomy
02 engineering and technology
Regulatory Sequences, Nucleic Acid
Monocytes
Mice
Epidermal growth factor
lcsh:Science
RAW 264.7 Cells
Sequence Deletion
Regulation of gene expression
Mice, Knockout
Myelopoiesis
Multidisciplinary
Microglia
musculoskeletal, neural, and ocular physiology
Cell Differentiation
021001 nanoscience & nanotechnology
Cell biology
medicine.anatomical_structure
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Female
Genetics & genetic processes [F10] [Life sciences]
0210 nano-technology
Génétique & processus génétiques [F10] [Sciences du vivant]
Phagocytosis
Science
Biology
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
medicine
Animals
Progenitor cell
Embryonic Stem Cells
Monocytes and macrophages
Cell Proliferation
Base Sequence
Epidermal Growth Factor
Macrophage Colony-Stimulating Factor
Macrophages
General Chemistry
Genes, fms
Embryonic stem cell
Mice, Inbred C57BL
Disease Models, Animal
Gene regulation in immune cells
030104 developmental biology
Gene Expression Regulation
nervous system
lcsh:Q
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Vol 10, Iss 1, Pp 1-17 (2019), Nature Communications, 10. NATURE PUBLISHING GROUP, Nature Communications, Rojo, R, Raper, A, Ozdemir, D D, Lefevre, L, Grabert, K, Wollscheid-Lengeling, E, Bradford, B, Caruso, M, Gazova, I, Sanchez, A, Lisowski, Z M, Alves, J, Molina-Gonzalez, I, Davtyan, H, Lodge, R J, Glover, J D, Wallace, R, Munro, D A D, David, E, Amit, I, Miron, V E, Priller, J, Jenkins, S J, Hardingham, G E, Blurton-Jones, M, Mabbott, N A, Summers, K M, Hohenstein, P, Hume, D A & Pridans, C 2019, ' Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. ', Nature Communications, vol. 10, 3215 . https://doi.org/10.1038/s41467-019-11053-8
- Accession number :
- edsair.doi.dedup.....8c3693a39f65abf35033f4274fb63d13