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Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System | Mononuclear Phagocyte Immunobiology Group

Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System

Date Published:

Jul 21

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.

Notes:

Bruttger, JuliaKarram, KhaladWortge, SimoneRegen, TommyMarini, FedericoHoppmann, NicolaKlein, MatthiasBlank, ThomasYona, SimonWolf, YochaiMack, MatthiasPinteaux, EmmanuelMuller, WernerZipp, FraukeBinder, HaraldBopp, TobiasPrinz, MarcoJung, SteffenWaisman, AriengG0801296/Medical Research Council/United KingdomResearch Support, Non-U.S. Gov'tImmunity. 2015 Jul 21;43(1):92-106. doi: 10.1016/j.immuni.2015.06.012. Epub 2015 Jul 7.