Microglia play an important role in normal brain functioning, and their impairment can contribute to neurological diseases.

Researchers have attempted to create microglia-like cells derived from human stem cells grown in culture, but these in vitro differentiated microglia-like cells show significant morphological and gene expression differences compared with primary microglia in the brain.

To replicate primary human microglia, the authors transplanted microglia precursors derived in vitro from human stem cells into neonatal mouse brains. The transplanted cells acquired characteristic microglial morphology and gene expression, including higher levels of microglial signature genes such as P2RY12, TMEM119, and BIN1 compared with in vitro cultured cells.

The transplanted cells closely resembled healthy primary microglia in the human brain, whereas in vitro cultured microglia resembled microglia in a diseased state and showed an upregulation of disease-associated genes.

Single-cell RNA-seq analysis of the transplanted microglia revealed similar cellular heterogeneity as primary microglia in the human brain. Transplanted microglia were converted to an activated state by lipopolysaccharide, showing a similar response to signals as primary resting microglia.

The authors conclude that growing microglial precursors in the mouse brain creates cells that closely resemble primary human microglia and suggest that these cells could serve as useful tools for studying human diseases.

https://www.pnas.org/content/early/2019/11/25/1913541116