PAX6-positive microglia evolve locally in hiPSC-derived ocular organoids [scRNA-Seq]

PAX6-positive microglia like cell 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 indicate that microglia-like cells, which have characteristics of yolk sac-like linage cells, naturally develop in two-dimensional eye-like SEAM organoids, which lack any vascular components. These cells are unique in that they are paired box protein 6 (PAX6) positive, yet 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.