 Microglia are increasingly implicated in brain pathology, particularly neurodegenerative diseases such as Alzheimer's, Parkinson's, and motor neuron disease. To better understand these diseases, there is a need for authentic, efficient in vitro models to study human microglial pathological mechanisms. Embryonic MYB-independent IPSC-derived macrophages can be differentiated into microglia, which can then be co-cultured with IPSC-derived cortical neurons. This co-culture retains neuronal maturity and functionality for many weeks, and microglia express key microglia-specific markers and neurodegenerative disease-relevant genes. They also develop highly dynamic ramifications and release multiple microglia-relevant cytokines upon activation. Furthermore, this co-culture promotes a more anti-inflammatory and pro-remodeling cytokine response than corresponding monocultures, demonstrating that co-cultures are preferable for modeling authentic microglial physiology. This article was authored by Walter Hensler, Stephen N. Sandsam, Julian Buchrezer, and others. We are article.tv, links in the description below.