1.7m mouse brain cells, 90% of genes mapped to 3D brain atlas

It’s a mind map – literally. American scientists have created a comprehensive ‘atlas’ of a mouse brain and they say one for the human organ isn’t far behind.

The map separates thousands of cell populations across the mouse brain and is believed to have successfully imaged around 90% of all cell types found within the animal’s ‘grey matter’.

Creating an ‘atlas’ for a mouse brain provides geneticists with a useful tool to identify cells for further study – including neurotransmitters and disease-causing genes – and where they are located in the brain.

The team from the Broad Institute of MIT and Harvard in the US used spatial transcriptomics – a process that identifies the protein-making genes within an organism’s genome and plots their location – using a technique developed in the lead authors’ laboratories.

An illustration of a brain atlas
In this visualization, 101 slices of brain tissue are stacked to illustrate coverage of known major regions of the mouse brain, shown in different colors for reference. Credit: Macosko and Chen labs, Broad Institute of MIT and Harvard.

The process, known as ‘slide-seq’ enables slides coated in a layer of microparticles each tagged with a unique DNA barcode to act as a kind of genetic GPS for thin layers of organ tissue. In this case a mouse brain was cut into 101 layers – about the thickness of a single cell – which were stuck to individual slides.

The genes were then transcribed and sequenced in order, with each gene’s location aligned to a pre-existing reference map. In total more than 1.7 million brain cells were mapped.

“Our atlas represents the culmination of a decade of work at the Broad [Institute],” says the senior author of the study Associate Professor Evan Macosko, a psychiatrist at Massachusetts General Hospital.

“Fei [Chen, the study’s co-leader] and I developed the technology in our labs and used it to process the largest single-cell and spatial dataset ever generated, leading to the first comprehensive atlas of cell types in a mammalian brain.”

Published today in the journal Nature, the brain atlas from Macosko and Chen’s labs is one of a set of 10 studies that investigate the mapping of the nervous system in mice.

The researchers say these studies are a step towards mapping the brain in humans, using a series of RNA sequencing techniques that will likely be used in efforts to map more complex mammal brains. The data produced by their mouse brain is available online.

“By mapping the mouse brain, the primary mammalian system used in neuroscience, we’ve provided molecular, functional, and anatomical classifications that provide a key foundation for human brain mapping, which is what comes next,” Macosko says.

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