hPSC-derived microglia shape neuronal morphology and enhance network activity in vitro 167 5 Figure 5: Co-cultures with 4H microglia-like cells do not show detectable differences compared to control microglia-like cell co-cultures A) Quantification of nuclear debris (A), mature NeuN positive neurons (B), axonal (C) and dendritic segments (D) was not significantly different between co-cultures with 4H and control microglia-like cells (p=0.836, Fisher’s method). Larger circles denote control (gray) and 4H (blue) group means and smaller symbols indicating observations per line on different time points (circles: 8 weeks post plating of neurons (WPP), triangles: 10 WPP, squares: 12 WPP). E) Comparison of mean active channels over time (7–12 WPP) in 4H (blue) and control microglia-like cell (gray) co-cultures. CONCLUSION / DISCUSSION: In this study, we developed an in vitro co-culture model integrating hPSC-derived microglialike cells and neurons, providing a more physiologically relevant system to investigate neuron-glia interactions. Our results show that the hPSC-derived microglia-like cells actively incorporate into the neuronal networks, influencing both neuronal morphology and network activity, which mirrors several known in vivo functions of microglia. Additionally, we did not observe differences in intrinsic microglia pathology as displayed by similar numbers and roundness between microglia-like cells of control and leukodystrophy iPSC-lines. However, we did identify show that ALD microglia-like cells had a different effect on axonal morphology compared to control microglia-like cells. This model offers a valuable tool for future studies to explore neuron-glia interactions in the context of neurodevelopmental and neurodegenerative disorders.
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