Here, we describe an efficient method to generate microglia-like cells from human ES and iPS cells representing a collection of control and disease subjects. Using recent insights into microglial differentiation 12, we show that microglia-like cells can be efficiently generated and enriched from multiple ES and iPS cell lines. Expression signatures of these pluripotent stem cell-derived microglia resemble those of purified human fetal microglia maintained in the same culture conditions and recapitulate the recently defined consensus signature of microglia compared to other macrophages 13,10,11. They perform the functions of professional phagocytes, are positive for microglial markers such as TMEM119, and react to canonical stimuli. Our results provide a system to study the maturation and steady-state behavior of human microglia in a highly defined cellular environment, and their involvement in disease onset, propagation and resolution.
