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A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.

Publication ,  Journal Article
Bennett, FC; Bennett, ML; Yaqoob, F; Mulinyawe, SB; Grant, GA; Hayden Gephart, M; Plowey, ED; Barres, BA
Published in: Neuron
June 27, 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.

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Published In

Neuron

DOI

EISSN

1097-4199

Publication Date

June 27, 2018

Volume

98

Issue

6

Start / End Page

1170 / 1183.e8

Location

United States

Related Subject Headings

  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Knockout
  • Mice
  • Macrophages
  • Humans
  • Hematopoietic Stem Cells
  • Central Nervous System
  • Cell Lineage
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bennett, F. C., Bennett, M. L., Yaqoob, F., Mulinyawe, S. B., Grant, G. A., Hayden Gephart, M., … Barres, B. A. (2018). A Combination of Ontogeny and CNS Environment Establishes Microglial Identity. Neuron, 98(6), 1170-1183.e8. https://doi.org/10.1016/j.neuron.2018.05.014
Bennett, F Chris, Mariko L. Bennett, Fazeela Yaqoob, Sara B. Mulinyawe, Gerald A. Grant, Melanie Hayden Gephart, Edward D. Plowey, and Ben A. Barres. “A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.Neuron 98, no. 6 (June 27, 2018): 1170-1183.e8. https://doi.org/10.1016/j.neuron.2018.05.014.
Bennett FC, Bennett ML, Yaqoob F, Mulinyawe SB, Grant GA, Hayden Gephart M, et al. A Combination of Ontogeny and CNS Environment Establishes Microglial Identity. Neuron. 2018 Jun 27;98(6):1170-1183.e8.
Bennett, F. Chris, et al. “A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.Neuron, vol. 98, no. 6, June 2018, pp. 1170-1183.e8. Pubmed, doi:10.1016/j.neuron.2018.05.014.
Bennett FC, Bennett ML, Yaqoob F, Mulinyawe SB, Grant GA, Hayden Gephart M, Plowey ED, Barres BA. A Combination of Ontogeny and CNS Environment Establishes Microglial Identity. Neuron. 2018 Jun 27;98(6):1170-1183.e8.
Journal cover image

Published In

Neuron

DOI

EISSN

1097-4199

Publication Date

June 27, 2018

Volume

98

Issue

6

Start / End Page

1170 / 1183.e8

Location

United States

Related Subject Headings

  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Knockout
  • Mice
  • Macrophages
  • Humans
  • Hematopoietic Stem Cells
  • Central Nervous System
  • Cell Lineage