Microglia mediate synaptic pruning during adolescence (Paolicelli et al., 2011) (although see Sekar et al., 2016 for neuronal contribution to synaptic pruning in SZ) and respond to immune threats by producing inflammatory cytokines (Kreutzberg, 1996); accordingly, abnormal pruning (Feinberg, 1982) and neuroinflammation (Ashdown et al., 2005; Monji et al., 2013) are thought to contribute to the etiology of SZ. Studying these functions in a hiPSC system would allow scientists to mix and match patient and control microglia and neurons, in order to determine the driving force behind abnormal cellular connectivity and function. Critically, microglia-like cells have been successfully generated from hiPSCs by several groups in the last year (Muffat et al., 2016; Abud et al., 2017; Pandya et al., 2017). These cells resemble fetal and adult human microglia in their gene expression patterns and show phagocytic activity in vitro and in vivo. A co-culture application for modeling synaptic pruning would benefit from more mature, myelinated neurons; however, hiPSC microglia show potential for modeling inflammatory activation early in development in a co-culture system.
