1. Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System.
- Author
-
Bruttger, Julia, Karram, Khalad, Wörtge, Simone, Regen, Tommy, Marini, Federico, Hoppmann, Nicola, Klein, Matthias, Blank, Thomas, Yona, Simon, Wolf, Yochai, Mack, Matthias, Pinteaux, Emmanuel, Müller, Werner, Zipp, Frauke, Binder, Harald, Bopp, Tobias, Prinz, Marco, Jung, Steffen, and Waisman, Ari
- Subjects
- *
CENTRAL nervous system , *MICROGLIA , *EMBRYOLOGY , *MACROPHAGES , *INTERLEUKIN-1 receptors , *GENE expression , *CELL proliferation , *ANATOMY , *THERAPEUTICS , *MAMMALS - Abstract
Summary 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF