Related Experiment Video
Updated: Oct 6, 2025
Generation of Human Microglia to Combine Them with Retinal Organoids for Improved Disease Modeling
Published on: July 26, 2024
PAX6-positive microglia evolve locally in hiPSC-derived ocular organoids
Nobuhiko Shiraki1, Kazuichi Maruyama2, Ryuhei Hayashi3
1Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
Abstract:
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.
Insights
Microglia, the immune cells of the central nervous system (CNS), develop within the eye. These microglia-like cells arise independently of the body’s vascular and immune systems in developing eye organoids.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia are the primary immune cells within the central nervous system (CNS).
- The retina is considered part of the CNS, but the developmental origins of ocular microglia remain unclear.
- Understanding ocular immune cell development is crucial for neuroinflammation research.
Purpose of the Study:
- To investigate the development of microglia within the eye.
- To determine if ocular microglia development is independent of systemic factors.
- To model early human eye development using stem cells.
Main Methods:
- Utilized human-induced pluripotent stem cells (hiPSCs) to create self-formed ectodermal autonomous multi-zone (SEAM) organoids.
- Cultured 2D eye-like SEAM organoids to mimic aspects of human eye development.
- Analyzed the characteristics and lineage of developing immune cells within the organoids.
Main Results:
- Microglia-like cells naturally developed within the SEAM eye organoids.
- These cells exhibited characteristics of yolk-sac lineage cells and were PAX6-positive.
- The developing ocular immune cells were present in organoids lacking vascular components.
- These cells showed some mesodermal characteristics, despite being PAX6-positive.
Conclusions:
- The eye possesses an intrinsic, locally developing immune system.
- Ocular microglia development appears independent of the body's vasculature and systemic immune system.
- SEAM organoids provide a valuable model for studying early ocular immune development.
