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@ARTICLE{Panagiotakopoulou:283103,
      author       = {Panagiotakopoulou, Vasiliki and Welzer, Marc and Ormaechea,
                      Olmo Ruiz and Werner, Diana and Erlebach, Lena and Bühler,
                      Anika and Obermüller, Ulrike and Neher, Jonas J and Jucker,
                      Mathias and Kronenberg-Versteeg, Deborah},
      title        = {{C}himeric human organoid and mouse brain slice co-cultures
                      to study microglial function.},
      journal      = {Cell reports},
      volume       = {44},
      number       = {12},
      issn         = {2211-1247},
      address      = {Maryland Heights, MO},
      publisher    = {Cell Press},
      reportid     = {DZNE-2025-01510},
      pages        = {116656},
      year         = {2025},
      abstract     = {Studying the dynamic role of microglia in brain development
                      and neurodegenerative diseases requires models that closely
                      resemble the human brain environment. While human induced
                      pluripotent stem cell (iPSC)-derived organoids (hORGs)
                      effectively reproduce key neuronal and certain glial cell
                      types, modeling human microglia in vitro remains
                      challenging. Inspired by recent approaches demonstrating
                      enhanced microglial maturation in hORGs transplanted into
                      mouse brains, we develop a chimeric model by co-culturing
                      hORGs with mouse brain slice cultures (mBSCs). This system
                      reveals cross-species interactions associated with an
                      earlier onset of cortical neuronal differentiation markers
                      in the hORGs. Human iPSC-derived microglia,
                      pre-differentiated in mBSCs, migrate into the hORGs and
                      adopt ramified morphology. They remain viable for several
                      months and respond to laser-induced injury, demonstrating
                      long-term functionality. This in vitro model supports
                      long-term study of human microglia in a brain-like
                      environment, providing a platform for mechanistic studies
                      and screening compounds that target microglial function.},
      keywords     = {Animals / Microglia: cytology / Microglia: metabolism /
                      Humans / Organoids: cytology / Organoids: metabolism /
                      Brain: cytology / Brain: metabolism / Coculture Techniques:
                      methods / Induced Pluripotent Stem Cells: cytology / Induced
                      Pluripotent Stem Cells: metabolism / Mice / Cell
                      Differentiation / Neurons: cytology / Neurons: metabolism /
                      CP: neuroscience (Other) / CP: stem cell research (Other) /
                      cerebral organoids (Other) / chimeric in vitro model (Other)
                      / human microglia (Other) / xenotransplantation (Other)},
      cin          = {AG Kronenberg-Versteeg / AG Jucker / AG Neher (Tübingen)},
      ddc          = {610},
      cid          = {I:(DE-2719)1210015 / I:(DE-2719)1210001 /
                      I:(DE-2719)1210012},
      pnm          = {351 - Brain Function (POF4-351) / 352 - Disease Mechanisms
                      (POF4-352)},
      pid          = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41385370},
      doi          = {10.1016/j.celrep.2025.116656},
      url          = {https://pub.dzne.de/record/283103},
}