Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse...

Area of Science:

• Neuroscience
• Stem Cell Biology
• Immunology

Background:

• Microglia are crucial for brain health, and their dysfunction is linked to neurological disorders.
• Current methods for deriving microglia-like cells from human induced pluripotent stem cells (hiPSCs) result in cells with altered morphology and gene expression compared to primary microglia.
• In vitro cultured microglia may not accurately represent the state of resting primary microglia.

Purpose of the Study:

• To develop a more accurate in vitro model of human microglia for disease research.
• To investigate whether transplanted hiPSC-derived microglia precursors can acquire a phenotype similar to primary human microglia in vivo.

Main Methods:

• Derived microglial precursors from hiPSCs.
• Transplanted these precursors into neonatal mouse brains.
• Analyzed cell morphology, gene expression, and cellular heterogeneity using single-cell RNA-sequencing.

Main Results:

• Transplanted hiPSC-derived microglia precursors adopted characteristic microglial morphology and gene expression profiles.
• The in vivo-generated microglia closely resembled primary human microglia.
• Single-cell RNA-sequencing revealed cellular heterogeneity in transplanted microglia comparable to primary human cells.

Conclusions:

• Transplantation into the neonatal mouse brain allows hiPSC-derived microglia to achieve a phenotype and gene expression signature similar to resting primary human microglia.
• This hiPSC-microglia chimera model provides a valuable tool for studying human microglia in the context of neurological diseases.