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

444 Scopus citations

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 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 languageAmerican English
Pages (from-to)92-106
Number of pages15
JournalImmunity
Volume43
Issue number1
DOIs
StatePublished - 21 Jul 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

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