EDITOR'S CHOICE IN NEUROSCIENCE
H. Zeng et al., “Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures,” Cell, 149:48-96, 2012.
Whole-genome sequencing has given researchers a good sense of which genes are shared between, for example, humans and mice. But little is known about how the expression patterns of these genes differ. Hongkui Zeng of the Allen Institute for Brain Science in Seattle, Washington, and colleagues took slices of human brains collected from postmortem biopsies and tested the expression of 1,000 key neuronal genes. They found that about 21 percent of the gene-expression profiles differed between the two species.
Researchers took thin slices from regions of the brain involved in processing visual and sensory information and scanned them for the in situ expression of 1,000 genes that act as markers of cell type or are involved in disease, evolution, or cortical function. They compared gene expression of three areas of the cortex across 46 donors with corresponding mouse-brain slices, which had been analyzed previously at the Allen Institute.
The differences between humans and mice “often manifested in a cell type-specific way,” said Zeng, or involved in between-cell communications. “The disease genes are all very well conserved,” which bodes well for researchers using mice as models of disease, she says.
“The mouse model is used extensively in neuroscience research, and it’s assumed to be a surrogate for the human,” says Daniel Geschwind, a neurogeneticist at the University of California, Los Angeles. Knowing the specific differences “gives you a sense that many things are conserved, but also provides some guidance as to the ones that aren’t.”