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Proc Natl Acad Sci U S A. 2019 Dec 10;116(50):25293-25303. doi: 10.1073/pnas.1913541116. Epub 2019 Nov 26.

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

Author information

Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Bioinformatics and Research Computing, Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Broad Institute of MIT and Harvard, Cambridge, MA 02142.
The Jackson Laboratory Cancer Center, The Jackson Laboratory, Bar Harbor, ME 04609.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.


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.


CSF1; P2RY12; RNA-seq; chimera; microglia


Conflict of interest statement

The authors declare no competing interest.

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