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An environment-dependent transcriptional network specifies human microglia identity

2017· article· en· 1,311 citations· W2619332462 on OpenAlex· 10.1126/science.aal3222

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Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

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Abstract

Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Science
Topic
Neuroinflammation and Neurodegeneration Mechanisms
Field
Neuroscience
Canadian institutions
Funders
National Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesUniversity of California, San DiegoNational Cancer InstituteNational Institutes of HealthCanadian Institutes of Health ResearchMultiple Sclerosis SocietyMultiple Sclerosis Society of Canada
Keywords
MicrogliaEpigeneticsBiologyGeneImmune systemEx vivoGene expressionFunction (biology)PhenotypeIn vitroNeuroscienceHuman brainCell biologyImmunologyGeneticsInflammation
Has abstract in OpenAlex
yes