TY  - JOUR
AU  - Kikhia, Majed
AU  - Schilling, Simone
AU  - Herzog, Marie-Louise
AU  - Livne, Michelle
AU  - Semtner, Marcus
AU  - Tay, Tuan Leng
AU  - Prinz, Marco
AU  - Kettenmann, Helmut
AU  - Endres, Matthias
AU  - Kronenberg, Golo
AU  - Göttert, Ria
AU  - Gertz, Karen
TI  - Multicolor fate mapping of microglia reveals polyclonal proliferation, heterogeneity, and cell-cell interactions after ischemic stroke in mice.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-01101
SP  - 8294
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Microglia: pathology
KW  - Microglia: physiology
KW  - Microglia: metabolism
KW  - Microglia: cytology
KW  - Cell Proliferation
KW  - Female
KW  - Ischemic Stroke: pathology
KW  - Ischemic Stroke: metabolism
KW  - Mice
KW  - Cell Communication: physiology
KW  - Mice, Inbred C57BL
KW  - Brain Ischemia: pathology
KW  - Disease Models, Animal
KW  - Stroke: pathology
KW  - Patch-Clamp Techniques
LB  - PUB:(DE-HGF)16
C6  - pmid:40957877
C2  - pmc:PMC12441135
DO  - DOI:10.1038/s41467-025-63949-3
UR  - https://pub.dzne.de/record/281354
ER  -