Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling...

Area of Science:

• Neuroscience
• Stem Cell Biology
• Developmental Biology

Background:

• Microglia are crucial for brain function, development, and disease.
• Animal models inadequately represent human microglia due to significant differences.
• Existing brain organoid models lack sufficient or properly timed human microglia integration.

Purpose of the Study:

• To develop an optimized brain organoid model incorporating human microglia.
• To enable the study of human microglia in a context mimicking in vivo development.
• To investigate human microglial functions and responses in neurological disease contexts.

Main Methods:

• Co-culturing human pluripotent stem cell (hPSC)-derived primitive neural progenitor cells and primitive macrophage progenitors.
• Generating brain region-specific organoids containing controlled numbers of human microglia.
• Assessing microglial phagocytic activity, synaptic pruning, and response to viral infection within organoids.

Main Results:

• Successfully generated a brain organoid model with tunable human microglia populations.
• Demonstrated that integrated human microglia possess phagocytic and synaptic pruning capabilities.
• Observed human microglial responses to Zika virus infection within the organoid system.

Conclusions:

• Established a new, microglia-containing human brain organoid model.
• This model provides a platform for studying human microglia in health and disease.
• Facilitates research into neurological disorders by overcoming animal model limitations.