Title

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

Document Type

Article

Publication Date

12-10-2019

Keywords

JMG

JAX Source

Proc Natl Acad Sci U S A 2019 Dec 10; 116(50):25293-25303

PMID

31772018

DOI

https://doi.org/10.1073/pnas.1913541116

Grant

OD26440,AI32963,CA034196

Abstract

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.

Share

COinS