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Science. 2017 Jun 23;356(6344). pii: eaal3222. doi: 10.1126/science.aal3222. Epub 2017 May 25.

An environment-dependent transcriptional network specifies human microglia identity.

Author information

1
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.
2
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1002, USA.
3
Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.
4
Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
5
Department of Neurosurgery, University of California, San Diego-Rady Children's Hospital, San Diego, CA 92123, USA.
6
Neuroimmunology, Biogen, 225 Binney Street, Cambridge, MA 02142, USA.
7
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA. ckg@ucsd.edu.
8
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.

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.

PMID:
28546318
PMCID:
PMC5858585
DOI:
10.1126/science.aal3222
[Indexed for MEDLINE]
Free PMC Article

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