Direct Reprogramming of Microglia into Neurons

In recent years, direct reprogramming methods have attracted attention as they can bypass the immature stem cell state and directly induce the desired cell type by introducing key transcription factors into somatic cells. This technique offers advantages such as shorter induction times compared to inducing the desired cells from induced pluripotent stem cells. Furthermore, this approach enables the provision of the requisite cell types to patients requiring treatment without eliciting an immune rejection response. Microglia, the resident immune cells of the central nervous system, exhibit high proliferative and regenerative capacities, allowing them to repopulate even after almost complete depletion. In response to injury, microglia accumulate in damaged brain regions and become the primary cell type that forms the glial scar. Given these properties, microglia are promising candidates for direct reprogramming into neurons in the injured area without depleting cell sources. This chapter outlines a protocol for directly reprogramming cortical microglia into neurons, utilizing primary culture and lentiviral-mediated gene transfer techniques.