Neuron-glia interactions using iAssembloids
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Using a 3D co-culture system of iPSCderived neurons and glia, termed iAssembloids, combined with CRISPRi based screening, the researchers investigate the effect of glial cells on neuronal activity and survival.
Using CRISPRi-based screens the authors identified that GSK3β inhibits the protective NRF2-mediated oxidative stress response elicited by high neuronal activity.
They also investigated the role of APOE-ε4, a risk variant for Alzheimer’s disease, on neuronal survival and demonstrate that APOE-ε4-expressing astrocytes may promote neuronal hyperactivity as compared with APOE-ε3-expressing astrocytes.
This platform allows for the unbiased identification of mechanisms of neuron-glia cell interactions.