A Core Transcription Regulatory Circuitry Defining Microglia Cell Identity Inferred from the Reanalysis of Multiple Human Microglia Differentiation Protocols

Microglia, the immune cells in the brain involved in both homeostasis and injury/infection control, play a predominant role in neurodegenerative diseases. In vivo studies on microglia are limited due to the requirement of surgical intervention, which can lead to the destruction of the tissues. Over the last few years, multiple protocols—presenting a variety of strategies—have described microglia differentiation issued from human pluripotent stem cells. Herein, we have reanalyzed the transcriptomes released on six different microglia differentiation protocols and revealed a consensus core of master transcription regulatory circuitry defining microglia identity. Furthermore, we have discussed the major divergencies among the studied protocols and have provided suggestions to further enhance microglia differentiation assays.