Abstract
The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B*) project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.
Highlights
The adult mammalian brain is one of the most sophisticated and complex organs devised by nature
To ensure the accuracy of our spatial expression dataset, we took samples of the central nervous system (CNS) regions every 4 hours, starting at ZT0 (Zeitgaber time 0; the time of lights on), for 24 hours (6 time-point samples for each region) to avoid potential artifacts caused by the circadian regulation of gene expression
Even for mis-clustered replicates of CNS regions, when we used an appropriate set of regional marker genes (e.g. Myl4) retrieved from other in situ databases, their expression patterns in our data resource could correctly distinguish them
Summary
The adult mammalian brain is one of the most sophisticated and complex organs devised by nature. DNA-microarray technology is an alternative way to obtain quantitative genomewide expression data in tissues and cell culture [22,23] This technology is widely used in biological research, including in neuroscience, and several groups have published resources showing transcript expression profiles in areas of the mammalian brain [10,11,12,13,14,15,16,17]. These resources provide quantitative expression data, the size of each sampled region is relatively large to ensure that adequate volumes of RNA samples are collected, and multiple functional nuclei, loci, ganglia, or substantia are merged into a single sampled region
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