title: Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System.
abstract: During early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism's lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed high amounts of the interleukin-1 receptor (IL-1R), and treatment with an IL-1R antagonist during the repopulation phase impaired microglia proliferation. Hence, microglia have the potential for efficient self-renewal without the contribution of peripheral myeloid cells, and IL-1R signaling participates in this restorative proliferation process.
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bruttger
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Khalad
authors.initials: K
authors.lastname: Karram
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Wörtge
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Tommy
authors.initials: T
authors.lastname: Regen
authors.affiliation: Institute for Medical Biometry, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 69, 55131 Mainz, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Marini
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr.1, 55131 Mainz, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Hoppmann
authors.affiliation: Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr.1, 55131 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
authors.affiliation: Department of Neuropathology & BIOSS Centre for Biological Signaling Studies, University of Freiburg, Breisacher Str. 64, 79098 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blank
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Yona
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yochai
authors.initials: Y
authors.lastname: Wolf
authors.affiliation: Department for Internal Medicine, University Hospital, 93042 Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinteaux
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr.1, 55131 Mainz, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
authors.affiliation: Institute for Medical Biometry, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 69, 55131 Mainz, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Binder
authors.affiliation: Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr.1, 55131 Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.affiliation: Department of Neuropathology & BIOSS Centre for Biological Signaling Studies, University of Freiburg, Breisacher Str. 64, 79098 Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany. Electronic address: waisman@uni-mainz.de.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
mesh_terms: D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology*; D019707:Receptors, Chemokine / Q000235:genetics; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C587672:IL1B protein, mouse; C583355:IL1R1 protein, mouse; D053583:Interleukin-1beta; D019707:Receptors, Chemokine; D053573:Receptors, Interleukin-1 Type I; D014409:Tumor Necrosis Factor-alpha