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- W2001285655 endingPage "2443.e20" @default.
- W2001285655 startingPage "2443.e9" @default.
- W2001285655 abstract "Microglia form the immune system of the brain. Previous studies in cell cultures and animal models suggest altered activation states and cellular senescence in the aged brain. Instead, we analyzed 3 transcriptome data sets from the postmortem frontal cortex of 381 control individuals to show that microglia gene markers assemble into a transcriptional module in a gene coexpression network. These markers predominantly represented M1 and M1/M2b activation phenotypes. Expression of genes in this module generally declines over the adult life span. This decrease was more pronounced in microglia surface receptors for microglia and/or neuron crosstalk than in markers for activation state phenotypes. In addition to these receptors for exogenous signals, microglia are controlled by brain-expressed regulatory factors. We identified a subnetwork of transcription factors, including RUNX1, IRF8, PU.1, and TAL1, which are master regulators (MRs) for the age-dependent microglia module. The causal contributions of these MRs on the microglia module were verified using publicly available ChIP-Seq data. Interactions of these key MRs were preserved in a protein-protein interaction network. Importantly, these MRs appear to be essential for regulating microglia homeostasis in the adult human frontal cortex in addition to their crucial roles in hematopoiesis and myeloid cell-fate decisions during embryogenesis." @default.
- W2001285655 created "2016-06-24" @default.
- W2001285655 creator A5007452812 @default.
- W2001285655 creator A5021151726 @default.
- W2001285655 creator A5027867456 @default.
- W2001285655 date "2015-08-01" @default.
- W2001285655 modified "2023-10-11" @default.
- W2001285655 title "Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex" @default.
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