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Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

Soreq, L; UK Brain Expression Consortium, .; North American Brain Expression Consortium, .; Rose, J; Soreq, E; Hardy, J; Trabzuni, D; ... Ule, J; + view all (2017) Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging. Cell Reports , 18 (2) pp. 557-570. 10.1016/j.celrep.2016.12.011. Green open access

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Abstract

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.

Type: Article
Title: Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.12.011
Publisher version: http://dx.doi.org/10.1016/j.celrep.2016.12.011
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: RNA-seq, aging, brain, exon microarrays, gene expression, immunohistochemistry, machine learning, microglia, neurons, olgiodendrocytes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1536054
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