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Publication : A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.

First Author  Bennett FC Year  2018
Journal  Neuron Volume  98
Issue  6 Pages  1170-1183.e8
PubMed ID  29861285 Mgi Jnum  J:269393
Mgi Id  MGI:6268895 Doi  10.1016/j.neuron.2018.05.014
Citation  Bennett FC, et al. (2018) A Combination of Ontogeny and CNS Environment Establishes Microglial Identity. Neuron 98(6):1170-1183.e8
abstractText  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.
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