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

Julia Bruttger, Khalad Karram, Simone Wörtge, Tommy Regen, Federico Marini, Nicola Hoppmann, Matthias Klein, Thomas Blank, Simon Yona, Yochai Wolf, Matthias Mack, Emmanuel Pinteaux, Werner Müller, Frauke Zipp, Harald Binder, Tobias Bopp, Marco Prinz, Steffen Jung, Ari Waisman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 1week 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.

Original languageEnglish
Pages (from-to)92-106
Number of pages15
Issue number1
StatePublished - 21 Jul 2015
Externally publishedYes


FundersFunder number
International Graduate School of ImmunotherapyGRK) 1043
Medical Research CouncilG0801296
Deutsche ForschungsgemeinschaftFOR) 1336, SFB/TRR128 TP A07
Gemeinnützige Hertie-Stiftung
Sixth Framework ProgrammeMUGEN LSHG-CT-2005-005203


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