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Tytuł:
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A core transcriptional signature of human microglia: Derivation and utility in describing region-dependent alterations associated with Alzheimer's disease.
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Autorzy:
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Patir A; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom.
Shih B; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom.
McColl BW; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom.; UK Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh, United Kingdom.
Freeman TC; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom.
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Źródło:
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Glia [Glia] 2019 Jul; Vol. 67 (7), pp. 1240-1253. Date of Electronic Publication: 2019 Feb 13.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't; Review
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Język:
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English
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Imprint Name(s):
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Publication: New York, NY : Wiley-Liss
Original Publication: New York : Alan R. Liss, Inc., c1988-
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MeSH Terms:
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Alzheimer Disease/*genetics
Alzheimer Disease/*metabolism
Microglia/*metabolism
Transcriptome/*physiology
Alzheimer Disease/pathology ; Animals ; Central Nervous System/metabolism ; Central Nervous System/pathology ; Gene Expression Profiling/methods ; Gene Expression Profiling/trends ; Humans ; Mice ; Microglia/pathology
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Grant Information:
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BBS/E/D/20211551 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/J004227/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BBS/E/D/20211553 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; MR/M003833 United Kingdom MRC_ Medical Research Council; MR/L003384/1 United Kingdom MRC_ Medical Research Council; BBS/E/D/20211552 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/I001107/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; MR/M003833/1 United Kingdom MRC_ Medical Research Council
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Contributed Indexing:
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Keywords: Alzheimer's; aging; microglia; neurodegenerative disease; transcriptome
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Entry Date(s):
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Date Created: 20190214 Date Completed: 20200116 Latest Revision: 20240306
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Update Code:
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20240306
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DOI:
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10.1002/glia.23572
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PMID:
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30758077
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Growing recognition of the pivotal role microglia play in neurodegenerative and neuroinflammatory disorders has accentuated the need to characterize their function in health and disease. Studies in mouse have applied transcriptome-wide profiling of microglia to reveal key features of microglial ontogeny, functional profile, and phenotypic diversity. While similar, human microglia exhibit clear differences to their mouse counterparts, underlining the need to develop a better understanding of the human microglial profile. On examining published microglia gene signatures, limited consistency was observed between studies. Hence, we sought to derive a core microglia signature of the human central nervous system (CNS), through a comprehensive analysis of existing transcriptomic datasets. Nine datasets derived from cells and tissues, isolated from various regions of the CNS across numerous donors, were subjected independently to an unbiased correlation network analysis. From each dataset, a list of coexpressing genes corresponding to microglia was identified, with 249 genes highly conserved between them. This core signature included known microglial markers, and compared with other signatures provides a gene set specific to microglia in the context of the CNS. The utility of this signature was demonstrated by its use in detecting qualitative and quantitative region-specific alterations in aging and Alzheimer's disease. These analyses highlighted the reactive response of microglia in vulnerable brain regions such as the entorhinal cortex and hippocampus, additionally implicating pathways associated with disease progression. We believe this resource and the analyses described here, will support further investigations to the contribution of human microglia in CNS health and disease.
(© 2019 Wiley Periodicals, Inc.)