A new fate mapping system reveals context-dependent random or clonal expansion of microglia
Tay TL, Mai D, Dautzenberg J, Fernandez-Klett F, Lin G, Sagar , Datta M, Drougard A, Stempfl T, Ardura-Fabregat A, Staszewski O, Margineanu A, Sporbert A, Steinmetz LM, Pospisilik JA, Jung S, Priller J, Gruen D, Ronneberger O, Prinz M (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 20
Pages Range: 793-803
Journal Issue: 6
DOI: 10.1038/nn.4547
Abstract
Microglia constitute a highly specialized network of tissue-resident immune cells that is important for the control of tissue homeostasis and the resolution of diseases of the CNS. Little is known about how their spatial distribution is established and maintained in vivo. Here we establish a new multicolor fluorescence fate mapping system to monitor microglial dynamics during steady state and disease. Our findings suggest that microglia establish a dense network with regional differences, and the high regional turnover rates found challenge the universal concept of microglial longevity. Microglial self-renewal under steady state conditions constitutes a stochastic process. During pathology this randomness shifts to selected clonal microglial expansion. In the resolution phase, excess disease-associated microglia are removed by a dual mechanism of cell egress and apoptosis to re-establish the stable microglial network. This study unravels the dynamic yet discrete self-organization of mature microglia in the healthy and diseased CNS.
Involved external institutions
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
European Molecular Biology Laboratory (EMBL)
Germany (DE)
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics
Germany (DE)
Universität Regensburg
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Weizmann Institute of Science
Israel (IL)
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
European Molecular Biology Laboratory (EMBL)
Germany (DE)
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics
Germany (DE)
Universität Regensburg
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Weizmann Institute of Science
Israel (IL)
How to cite
APA:
Tay, T.L., Mai, D., Dautzenberg, J., Fernandez-Klett, F., Lin, G., Sagar, .,... Prinz, M. (2017). A new fate mapping system reveals context-dependent random or clonal expansion of microglia. Nature Neuroscience, 20(6), 793-803. https://doi.org/10.1038/nn.4547
MLA:
Tay, Tuan Leng, et al. "A new fate mapping system reveals context-dependent random or clonal expansion of microglia." Nature Neuroscience 20.6 (2017): 793-803.
BibTeX: Download