Nov 28, 2019

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

Proceedings of the National Academy of Sciences of the United States of America
Devon S SvobodaRudolf Jaenisch


Microglia are essential for maintenance of normal brain function, with dysregulation contributing to numerous neurological diseases. Protocols have been developed to derive microglia-like cells from human induced pluripotent stem cells (hiPSCs). However, primary microglia display major differences in morphology and gene expression when grown in culture, including down-regulation of signature microglial genes. Thus, in vitro differentiated microglia may not accurately represent resting primary microglia. To address this issue, we transplanted microglial precursors derived in vitro from hiPSCs into neonatal mouse brains and found that the cells acquired characteristic microglial morphology and gene expression signatures that closely resembled primary human microglia. Single-cell RNA-sequencing analysis of transplanted microglia showed similar cellular heterogeneity as primary human cells. Thus, hiPSCs-derived microglia transplanted into the neonatal mouse brain assume a phenotype and gene expression signature resembling that of resting microglia residing in the human brain, making chimeras a superior tool to study microglia in human disease.

  • References50
  • Citations2


  • References50
  • Citations2


Mentioned in this Paper

Pluripotent Stem Cells
Gene Expression
Human Cell Line
Induced Pluripotent Stem Cells
CNS - Brain (Mmhcc)
Sequence Analysis, RNA
Brain Function

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