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Publication

A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.

Neuron | 2018

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.

Pubmed ID: 29861285 RIS Download

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Associated grants

Agency: NIMH NIH HHS, United States
Id: T32 MH019938
Agency: NINDS NIH HHS, United States
Id: P30 NS069375
Agency: NCI NIH HHS, United States
Id: R01 CA216054
Agency: NIDA NIH HHS, United States
Id: R01 DA015043
Agency: NINDS NIH HHS, United States
Id: K08 NS085324
Agency: NIMH NIH HHS, United States
Id: L30 MH108106
Agency: NIDA NIH HHS, United States
Id: R37 DA015043
Agency: NIA NIH HHS, United States
Id: P50 AG047366
Agency: NINDS NIH HHS, United States
Id: K08 NS091527
Agency: NCRR NIH HHS, United States
Id: S10 RR025518
Agency: NIMH NIH HHS, United States
Id: K08 MH112120
Agency: NINDS NIH HHS, United States
Id: K08 NS075144
Agency: NINDS NIH HHS, United States
Id: F31 NS078813

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