1. Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling
- Author
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Tobias Goldmann, Fabio M.V. Rossi, Chotima Böttcher, Peipei Zhang, Jana Koch, Stefaniya Boneva, Ingo Hilgendorf, Ori Staszewski, Takahiro Masuda, Lukas Amann, Peter Wieghofer, Nora Hagemeyer, Josef Priller, Marco Prinz, Roman Sankowski, Clemens Lange, Annika Hausmann, Anja Schlecht, and Markus Gruber
- Subjects
Male ,retina ,Myeloid ,Transcription, Genetic ,genetic structures ,microglia ,Eye ,Macular Degeneration ,Mice ,0302 clinical medicine ,Homeostasis ,Macrophage ,Myeloid Cells ,0303 health sciences ,single-cell RNA-seq ,Microglia ,General Neuroscience ,Microbiota ,immunology [Macrophages] ,macrophages ,medicine.anatomical_structure ,Choroidal neovascularization ,genetics [Transcription, Genetic] ,physiology [Neovascularization, Physiologic] ,blood supply [Choroid] ,Female ,medicine.symptom ,Single-Cell Analysis ,Resource ,immunology [Eye] ,Immunology ,Neovascularization, Physiologic ,Mice, Transgenic ,Biology ,metabolism [Myeloid Cells] ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,Fate mapping ,ddc:570 ,metabolism [Eye] ,cornea ,immunology [Homeostasis] ,medicine ,Animals ,Humans ,Computer Simulation ,ddc:610 ,single‐cell RNA‐seq ,Molecular Biology ,030304 developmental biology ,Retina ,embryology [Choroid] ,Innate immune system ,General Immunology and Microbiology ,Choroid ,Sequence Analysis, RNA ,Macrophages ,Computational Biology ,cytology [Eye] ,Immunity, Innate ,eye diseases ,physiology [Microglia] ,immunology [Immunity, Innate] ,Mice, Inbred C57BL ,sense organs ,Neuroscience ,pathology [Macular Degeneration] ,030217 neurology & neurosurgery ,immunology [Myeloid Cells] - Abstract
Similar to the brain, the eye is considered an immune‐privileged organ where tissue‐resident macrophages provide the major immune cell constituents. However, little is known about spatially restricted macrophage subsets within different eye compartments with regard to their origin, function, and fate during health and disease. Here, we combined single‐cell analysis, fate mapping, parabiosis, and computational modeling to comprehensively examine myeloid subsets in distinct parts of the eye during homeostasis. This approach allowed us to identify myeloid subsets displaying diverse transcriptional states. During choroidal neovascularization, a typical hallmark of neovascular age‐related macular degeneration (AMD), we recognized disease‐specific macrophage subpopulations with distinct molecular signatures. Our results highlight the heterogeneity of myeloid subsets and their dynamics in the eye that provide new insights into the innate immune system in this organ which may offer new therapeutic targets for ophthalmological diseases., Single‐cell RNA‐sequencing reveals heterogeneity of macrophages in the cornea, ciliary body and retina under homeostatic conditions.
- Published
- 2021