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000283103 1001_ $$0P:(DE-2719)2813672$$aPanagiotakopoulou, Vasiliki$$b0$$eFirst author$$udzne
000283103 245__ $$aChimeric human organoid and mouse brain slice co-cultures to study microglial function.
000283103 260__ $$aMaryland Heights, MO$$bCell Press$$c2025
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000283103 520__ $$aStudying 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.
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000283103 650_7 $$2Other$$aCP: neuroscience
000283103 650_7 $$2Other$$aCP: stem cell research
000283103 650_7 $$2Other$$acerebral organoids
000283103 650_7 $$2Other$$achimeric in vitro model
000283103 650_7 $$2Other$$ahuman microglia
000283103 650_7 $$2Other$$axenotransplantation
000283103 650_2 $$2MeSH$$aAnimals
000283103 650_2 $$2MeSH$$aMicroglia: cytology
000283103 650_2 $$2MeSH$$aMicroglia: metabolism
000283103 650_2 $$2MeSH$$aHumans
000283103 650_2 $$2MeSH$$aOrganoids: cytology
000283103 650_2 $$2MeSH$$aOrganoids: metabolism
000283103 650_2 $$2MeSH$$aBrain: cytology
000283103 650_2 $$2MeSH$$aBrain: metabolism
000283103 650_2 $$2MeSH$$aCoculture Techniques: methods
000283103 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: cytology
000283103 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: metabolism
000283103 650_2 $$2MeSH$$aMice
000283103 650_2 $$2MeSH$$aCell Differentiation
000283103 650_2 $$2MeSH$$aNeurons: cytology
000283103 650_2 $$2MeSH$$aNeurons: metabolism
000283103 7001_ $$0P:(DE-2719)9000948$$aWelzer, Marc$$b1
000283103 7001_ $$0P:(DE-HGF)0$$aOrmaechea, Olmo Ruiz$$b2
000283103 7001_ $$0P:(DE-2719)9002990$$aWerner, Diana$$b3$$udzne
000283103 7001_ $$0P:(DE-2719)9000542$$aErlebach, Lena$$b4$$udzne
000283103 7001_ $$0P:(DE-2719)2813030$$aBühler, Anika$$b5$$udzne
000283103 7001_ $$0P:(DE-2719)2814201$$aObermüller, Ulrike$$b6
000283103 7001_ $$0P:(DE-2719)2811021$$aNeher, Jonas J$$b7$$udzne
000283103 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b8$$udzne
000283103 7001_ $$0P:(DE-2719)9001451$$aKronenberg-Versteeg, Deborah$$b9$$eLast author$$udzne
000283103 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2025.116656$$gVol. 44, no. 12, p. 116656 -$$n12$$p116656$$tCell reports$$v44$$x2211-1247$$y2025
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