Glia Open Access Database (GOAD): A comprehensive gene expression encyclopedia of glia cells in health and disease

Abstract

Recently, the number of genome-wide transcriptome profiles of pure populations of glia cells has drastically increased, resulting in an unprecedented amount of data that offer opportunities to study glia phenotypes and functions in health and disease. To make genome-wide transcriptome data easily accessible, we developed the Glia Open Access Database (GOAD), available via www.goad.education. GOAD contains a collection of previously published and unpublished transcriptome data, including datasets from isolated microglia, astrocytes and oligodendrocytes both at homeostatic and pathological conditions. It contains an intuitive web-based interface that consists of three features that enable searching, browsing, analyzing, and downloading of the data. The first feature is differential gene expression (DE) analysis that provides genes that are significantly up and down-regulated with the associated fold changes and p-values between two conditions of interest. In addition, an interactive Venn diagram is generated to illustrate the overlap and differences between several DE gene lists. The second feature is quantitative gene expression (QE) analysis, to investigate which genes are expressed in a particular glial cell type and to what degree. The third feature is a search utility, which can be used to find a gene of interest and depict its expression in all available expression data sets by generating a gene card. In addition, quality guidelines and relevant concepts for transcriptome analysis are discussed. Finally, GOAD is discussed in relation to several online transcriptome tools developed in neuroscience and immunology. In conclusion, GOAD is a unique platform to facilitate integration of bioinformatics in glia biology.

Astrocytic glycogen metabolism in the healthy and diseased brain

“…As expected if Ca 2+ and cAMP-PKA jointly activate PhK, the breakdown was curbed by inhibition of adenylate cyclases (ACs); since SOCE was induced separately from GPCR activation, this indicates that the breakdown is dependent on Ca 2+ -induced cAMP signaling, presumably by Ca 2+ -activated AC isoform 8 (AC8; Fig. 1), which is present in astrocytes (48,53). AC8 can be activated by SOCE in the absence of GPCR activation, perhaps in part due to a physical association with Orai1 channels (55)(56)(57), although the relative roles of TRPC vs. Orai channels for mediating SOCE remains controversial (58,59).…”

Cross-Laboratory Analysis of Brain Cell Type Transcriptomes with Applications to Interpretation of Bulk Tissue Data

“…Microglia expression profiles differ significantly between activated and inactivated states and to our knowledge, the samples in our database represent only the inactive state (Holtman et al, 2015). In order to acquire marker genes with stable expression levels regardless of microglia activation state, we removed the genes differentially expressed in activated microglia based on Holtman et al (2015).…”

“…In order to acquire marker genes with stable expression levels regardless of microglia activation state, we removed the genes differentially expressed in activated microglia based on Holtman et al (2015). This step resulted in removal of 408 out of the original 720 microglial genes in cortex (microarray and RNA-seq lists combined) and 253 of the 493 genes in the context of other brain regions (without genes from single-cell data).…”

Strategies for immunohistochemical protein localization using antibodies: What did we learn from neurotransmitter transporters in glial cells and neurons

“…It may be worthwhile to search available microarray, transcriptome and proteome datasets (e.g. Lu et al, 2009;Walther and Mann, 2011;Ulrich et al, 2014;Holtman et al, 2015) as these may give good indications of which proteins it may be possible to detect.…”