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Updated: May 20, 2026
Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue
Published on: August 15, 2012
Identification of secondary microglial formation centers in the human fetal brain
Chenyun Song1, Xinyu Chen1, Rong Ji2
1Department of Anatomy and Histology & Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Abstract:
Microglia migrate from the yolk sac and populate the developing brain. How microglia expand rapidly to meet the microglial demand in fast-expanding human fetal brains remains uncharted. Using thick sections in 5-22-gestational week (gw) brains and super-resolution scanning, we identified a large proliferative microglial aggregate (2.129 mm2) near the lateral ganglionic eminence (>12.5 gw), expanding in Down's syndrome (DS) (4.767 mm2) and Edwards syndrome (ES) (3.437 mm2) fetal brains. Ki67+ microglia within the aggregates accounted for 26.65% (DS: 38.9%; ES: 46.3%) compared with 6.32% (DS: 6.01%; ES: 5.2%) in scattered microglia. This aggregate region contained a distinct microglial population characterized by the absence of phagocytic structures and complex processes, high CSF-1R expression, abundant IL-34+ cells, and some SPP1+ bipolar microglia. We termed this structure the secondary microglial formation center (SMFC). Chimeric microglia-human cortical organoids recapitulated the SMFC in an IL-34- and CSF-1R-dependent manner, indicating that the human SMFC may compensate for the microglial shortage during the fastest expansion period.
Insights
Researchers discovered a novel microglial aggregate, the secondary microglial formation center (SMFC), in developing human brains. This structure rapidly expands to meet microglial needs, particularly in fetal brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia, the brain's resident immune cells, originate from the yolk sac and colonize the developing brain.
- The rapid expansion of microglia to meet the demands of fast-developing human fetal brains is not well understood.
Purpose of the Study:
- To investigate the mechanisms of microglial expansion in the developing human brain.
- To identify and characterize novel structures involved in microglial proliferation.
Main Methods:
- Super-resolution scanning of human fetal brain sections (5-22 gestational weeks).
- Analysis of microglial proliferation markers (Ki67) and cellular characteristics.
- In vitro studies using chimeric microglia-human cortical organoids.
Main Results:
- A large, proliferative microglial aggregate, termed the secondary microglial formation center (SMFC), was identified near the lateral ganglionic eminence.
- SMFCs were significantly larger in fetal brains with Down's syndrome (DS) and Edwards syndrome (ES).
- SMFCs showed high CSF-1R expression and abundant IL-34, with distinct microglial morphology and reduced phagocytic activity.
Conclusions:
- The SMFC is a novel structure crucial for rapid microglial expansion during human fetal brain development.
- The SMFC may play a role in neurodevelopmental disorders associated with altered microglial populations.
- IL-34 and CSF-1R signaling are critical for SMFC formation and function, potentially compensating for microglial shortages.
