TY - JOUR
T1 - Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling
AU - Wieghofer, Peter
AU - Hagemeyer, Nora
AU - Sankowski, Roman
AU - Schlecht, Anja
AU - Staszewski, Ori
AU - Amann, Lukas
AU - Gruber, Markus
AU - Koch, Jana
AU - Hausmann, Annika
AU - Zhang, Peipei
AU - Boneva, Stefaniya
AU - Masuda, Takahiro
AU - Hilgendorf, Ingo
AU - Goldmann, Tobias
AU - Böttcher, Chotima
AU - Priller, Josef
AU - Rossi, Fabio M.V.
AU - Lange, Clemens
AU - Prinz, Marco
N1 - Funding Information:
The authors thank Marc Leinweber, Gabriele Prinz, Maria Oberle, Johannes Baumann, Katrin Seidel, Eileen Barleon, Constance Hobusch, Angela Ehrlich, Heidrun Kuhrt, and Sylvia Zeitler for excellent technical assistance, M. Follo and team at lighthouse fluorescence technologies core Facility, University Medical Center, Freiburg for cell sorting, CEMT at University of Freiburg for excellent animal care, KFB, Center of Excellence for Fluorescent Bioanalytics, Regensburg for bulk RNA‐seq analysis, Jonas Neher, Tübingen (‐), Frédéric Geissmann, New York for providing ‐ mice. Special thanks to Sagar and Dominic Grün, MPI‐IE, Freiburg, for providing excellent support for scRNA‐seq. M.P. is supported by the Sobek Foundation, the Ernst‐Jung Foundation, the German Research Foundation (SFB 992, SFB1160, Reinhart‐Koselleck‐Grant, Gottfried Wilhelm Leibniz Prize) and the Ministry of Science, Research and Arts, Baden‐Wuerttemberg (Sonderlinie “Neuroinflammation”). His research is supported by the German Research Foundation (DFG) under Germany's Excellence Strategy (CIBSS—EXC‐2189—Project ID 390939984). J.P. received additional funding from the Berlin Institute of Health (CRG2aSP6), DFG (SFB/TRR265), and the UK DRI (Momentum Award). CL, MP, JP, CB and IH are supported by the SFB/TRR167. Open Access funding enabled and organized by ProjektDEAL. Ccr2 RFP Flt3 Cre :Rosa26 YFP
Funding Information:
The authors thank Marc Leinweber, Gabriele Prinz, Maria Oberle, Johannes Baumann, Katrin Seidel, Eileen Barleon, Constance Hobusch, Angela Ehrlich, Heidrun Kuhrt, and Sylvia Zeitler for excellent technical assistance, M. Follo and team at lighthouse fluorescence technologies core Facility, University Medical Center, Freiburg for cell sorting, CEMT at University of Freiburg for excellent animal care, KFB, Center of Excellence for Fluorescent Bioanalytics, Regensburg for bulk RNA-seq analysis, Jonas Neher, Tübingen (Ccr2-RFP), Frédéric Geissmann, New York for providing Flt3Cre:Rosa26-YFP mice. Special thanks to Sagar and Dominic Grün, MPI-IE, Freiburg, for providing excellent support for scRNA-seq. M.P. is supported by the Sobek Foundation, the Ernst-Jung Foundation, the German Research Foundation (SFB 992, SFB1160, Reinhart-Koselleck-Grant, Gottfried Wilhelm Leibniz Prize) and the Ministry of Science, Research and Arts, Baden-Wuerttemberg (Sonderlinie “Neuroinflammation”). His research is supported by the German Research Foundation (DFG) under Germany's Excellence Strategy (CIBSS—EXC-2189—Project ID 390939984). J.P. received additional funding from the Berlin Institute of Health (CRG2aSP6), DFG (SFB/TRR265), and the UK DRI (Momentum Award). CL, MP, JP, CB and IH are supported by the SFB/TRR167. Open Access funding enabled and organized by ProjektDEAL.
Publisher Copyright:
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license
PY - 2021/3/15
Y1 - 2021/3/15
N2 - 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.
AB - 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.
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U2 - 10.15252/embj.2020105123
DO - 10.15252/embj.2020105123
M3 - Article
C2 - 33555074
AN - SCOPUS:85100578540
SN - 0261-4189
VL - 40
JO - EMBO Journal
JF - EMBO Journal
IS - 6
M1 - e105123
ER -