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
ISSN
1091-6490
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.
Recommended Citation
Svoboda D,
Barrasa M,
Shu J,
Rietjens R,
Zhang S,
Mitalipova M,
Berube P,
Fu D,
Shultz LD,
Bell G,
Jaenisch R.
Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain. Proc Natl Acad Sci U S A 2019 Dec 10; 116(50):25293-25303