Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain
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25293.full.pdf
Description
Published version
Size
3.44 MB
Format
Adobe PDF
Checksum (MD5)
0c51dae51679b6094b97ddef3634590a
Author(s)
Svoboda, Devon S.
Barrasa, M. Inmaculada
Shu, Jian
Rietjens, Rosalie
Zhang, Shupei
Mitalipova, Maya
Berube, Peter
Fu, Dongdong
Shultz, Leonard D.
Bell, George W.
Date Issued
November 2019
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
Svoboda, Devon S. et al. "Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain." Proceedings of the National Academy of Sciences 116, 50 (November 2019): 25293-25303 © 2019 National Academy of Sciences
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1913541116
