Efficient derivation of microglia-like cells from human pluripotent stem cells
Name
nihms813405.pdf
Size
2.16 MB
Format
Adobe PDF
Checksum (MD5)
c86bff5d1d266e367523bc5826c9c6ed
Author(s)
Muffat, Julien
Li, Yun
Yuan, Bingbing
Mitalipova, Maisam
Omer, Attya
Bakiasi, Grisilda
Aubourg, Patrick
Ransohoff, Richard M
Corcoran, Sean R.
Tsai, Li-Huei
Date Issued
September 2016
Journal
Nature Medicine
Publisher
Nature Publishing Group
Citation
Muffat, Julien, et al. “Efficient Derivation of Microglia-Like Cells from Human Pluripotent Stem Cells.” Nature Medicine 22, 11 (September 2016): 1358–1367 © 2016 Nature America, Inc, part of Springer Nature
Version
Author's final manuscript
Abstract
Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts, and they resemble primary fetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines and find that pMGLs derived from an hES model of Rett syndrome are smaller than their isogenic controls. We further describe a platform to study the integration and live behavior of pMGLs in organotypic 3D cultures. This modular differentiation system allows for the study of microglia in highly defined conditions as they mature in response to developmentally relevant cues, and it provides a framework in which to study the long-term interactions of microglia residing in a tissue-like environment.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/NM.4189
