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@ARTICLE{Kikhia:281354,
      author       = {Kikhia, Majed and Schilling, Simone and Herzog,
                      Marie-Louise and Livne, Michelle and Semtner, Marcus and
                      Tay, Tuan Leng and Prinz, Marco and Kettenmann, Helmut and
                      Endres, Matthias and Kronenberg, Golo and Göttert, Ria and
                      Gertz, Karen},
      title        = {{M}ulticolor fate mapping of microglia reveals polyclonal
                      proliferation, heterogeneity, and cell-cell interactions
                      after ischemic stroke in mice.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DZNE-2025-01101},
      pages        = {8294},
      year         = {2025},
      abstract     = {Microglial proliferation is a principal element of the
                      inflammatory response to brain ischemia. However, the
                      precise proliferation dynamics, phenotype acquisition, and
                      functional consequences of newly emerging microglia are not
                      yet understood. Using multicolor fate mapping and
                      computational methods, we here demonstrate that microglia
                      exhibit polyclonal proliferation in the ischemic lesion of
                      female mice. The peak number of clones occurs at 14 days,
                      while the largest clones are observed at 4 weeks
                      post-stroke. Whole-cell patch-clamp recordings of microglia
                      reveal a homogeneous acute response to ischemia with a
                      pattern of outward and inward currents that evolves over
                      time. In the resolution phase, 8 weeks post-stroke,
                      microglial cells within one clone share similar membrane
                      properties, while neighboring microglia from different
                      clones display more heterogeneous electrophysiological
                      profiles. Super-resolution microscopy and live-cell imaging
                      unmask various forms of cell-cell interactions between
                      microglial cells from different clones. Overall, this study
                      demonstrates the polyclonal proliferation of microglia after
                      cerebral ischemia and suggests that clonality contributes to
                      their functional heterogeneity. Thus, targeting clones with
                      specific functional phenotypes may have potential for future
                      therapeutic modulation of microglia after stroke.},
      keywords     = {Animals / Microglia: pathology / Microglia: physiology /
                      Microglia: metabolism / Microglia: cytology / Cell
                      Proliferation / Female / Ischemic Stroke: pathology /
                      Ischemic Stroke: metabolism / Mice / Cell Communication:
                      physiology / Mice, Inbred C57BL / Brain Ischemia: pathology
                      / Disease Models, Animal / Stroke: pathology / Patch-Clamp
                      Techniques},
      cin          = {AG Endres},
      ddc          = {500},
      cid          = {I:(DE-2719)1811005},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40957877},
      pmc          = {pmc:PMC12441135},
      doi          = {10.1038/s41467-025-63949-3},
      url          = {https://pub.dzne.de/record/281354},
}