PAX6-positive microglia evolve locally in hiPSC-derived ocular organoids

Microglia are the resident immune cells of the central nervous system (CNS). They govern the immunogenicity of the retina, which is considered to be part of the CNS; however, it is not known how microglia develop in the eye. Here, we studied human-induced pluripotent stem cells (hiPSCs) that had been expanded into a self-formed ectodermal autonomous multi-zone (SEAM) of cells that partially mimics human eye development. Our results indicated that microglia-like cells, which have characteristics of yolk-sac-like linage cells, naturally develop in 2D eye-like SEAM organoids, which lack any vascular components. These cells are unique in that they are paired box protein 6 (PAX6)-positive, yet they possess some characteristics of mesoderm. Collectively, the data support the notion of the existence of an isolated, locally developing immune system in the eye, which is independent of the body’s vasculature and general immune system. •Eye-like organoids from hiPSCs contained immune cells similar to microglia cells•RNA-sequencing shows they have specific characteristic of microglia•Single-cell analyses indicate they resemble yol-sac-derived myeloid progenitors•These cells are unique in that they are PAX6- (eye master gene) positive immune cells Maruyama and colleagues (Shiraki et al.) discovered microglia-like cells in 2D eye-like organoids from hiPSCs. The cells show microglia characteristics and are PAX6-positive. Single-cell RNA sequencing further indicates that they resemble yolk-sac-derived myeloid progenitors and not macrophages. The 2D eye-like organoids with immune cells provide a useful experimental model of certain types of CNS structure, including the retina.