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A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.

Neuron (2018-06-05)
F Chris Bennett, Mariko L Bennett, Fazeela Yaqoob, Sara B Mulinyawe, Gerald A Grant, Melanie Hayden Gephart, Edward D Plowey, Ben A Barres
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-MS4A7 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Supelco
(S)-(−)-Sulpiride, VETRANAL®, analytical standard