Microglial ontogeny and in vitro reconstruction: Bridging development and modeling

Area of Science:

• Neuroimmunology
• Developmental Neuroscience
• Stem Cell Biology

Background:

• Microglia are unique CNS immune cells with a distinct yolk sac origin.
• Their development involves colonization, differentiation, and maturation influenced by the brain microenvironment.
• Understanding microglial ontogeny is crucial for central nervous system (CNS) research.

Purpose of the Study:

• To review the molecular and developmental mechanisms of microglial ontogeny.
• To discuss the advancements and applications of in vitro models for studying microglia.
• To highlight how integrated knowledge refines experimental systems for human disease research.

Main Methods:

• Review of current literature on microglial development and in vitro models.
• Analysis of progenitor specification, brain colonization, and maturation processes.
• Evaluation of human induced pluripotent stem cell (iPSC)-derived microglia and organoid models.

Main Results:

• Significant progress in elucidating microglial developmental pathways.
• Development of diverse in vitro systems, including iPSC-derived microglia, for disease modeling.
• Enhancement of physiological relevance through transplantation and organoid models.

Conclusions:

• In vitro models offer powerful, complementary platforms for studying microglial biology.
• Integrating developmental knowledge with in vitro systems advances CNS disease research.
• Further refinement of experimental systems is key to understanding microglial roles in health and disease.