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Neuron. 2018 Jun 27;98(6):1170-1183.e8. doi: 10.1016/j.neuron.2018.05.014. Epub 2018 May 31.

A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.

Author information

1
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: eph.bennett@gmail.com.
2
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

Microglia, the brain's resident macrophages, are dynamic CNS custodians with surprising origins in the extra-embryonic yolk sac. The consequences of their distinct ontogeny are unknown but critical to understanding and treating brain diseases. We created a brain macrophage transplantation system to disentangle how environment and ontogeny specify microglial identity. We find that donor cells extensively engraft in the CNS of microglia-deficient mice, and even after exposure to a cell culture environment, microglia fully regain their identity when returned to the CNS. Though transplanted macrophages from multiple tissues can express microglial genes in the brain, only those of yolk-sac origin fully attain microglial identity. Transplanted macrophages of inappropriate origin, including primary human cells in a humanized host, express disease-associated genes and specific ontogeny markers. Through brain macrophage transplantation, we discover new principles of microglial identity that have broad applications to the study of disease and development of myeloid cell therapies.

KEYWORDS:

Csf1r; Tmem119; brain macrophage; glial biology; microglia; neuroimmunity; ontogeny; transplantation

PMID:
29861285
PMCID:
PMC6023731
[Available on 2019-06-27]
DOI:
10.1016/j.neuron.2018.05.014

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