The mouse is the most commonly used vertebrate experimental model in neuroscience research, and the new atlas paves the way for a greater understanding of the human brain. The atlas describes the type, location, and molecular information of more than 32 million cells and provides information on connectivity between these cells.
Transcriptomic cell-type taxonomy of the whole mouse brain. Image credit: Yao et al., doi: 10.1038/s41586-023-06812-z.
“A cell’s DNA is like its language,” said Professor Bing Ren, a researcher at the University of California, San Diego.
“Just like there are certain root words that many languages share, there are certain genes and gene expression patterns that are conserved across different species.”
“Learning to understand and interpret the brain’s molecular language can help us learn more about how the brain works in general and about what happens to the brain in neuropsychiatric conditions.”
“The mouse atlas has brought the intricate network of mammalian brain cells into unprecedented focus, giving researchers the details needed to understand human brain function and diseases,” said Dr. Joshua Gordon, director of the National Institute of Mental Health, part of the National Institutes of Health.
The new atlas describes the types of cells in each region of the mouse brain and their organization within those regions.
In addition to this structural information, the cell atlas provides an incredibly detailed catalog of the cell’s transcriptome — the complete set of gene readouts in a cell, which contains instructions for making proteins and other cellular products.
The transcriptomic information included in the atlas is hierarchically organized, detailing cell classes, subclasses, and thousands of individual cell clusters within the brain.
The atlas also characterizes the cell epigenome — chemical modifications to a cell’s DNA and chromosomes that alter the way the cell’s genetic information is expressed — detailing thousands of epigenomic cell types and millions of candidate genetic regulation elements for different brain cell types.
Together, the structural, transcriptomic, and epigenetic information included in this atlas provide an unprecedented map of cellular organization and diversity across the mouse brain.
The atlas also provides an accounting of the neurotransmitters and neuropeptides used by different cells and the relationship among cell types within the brain.
This information can be used as a detailed blueprint for how chemical signals are initiated and transmitted in different parts of the brain.
Those electrical signals are the basis for how brain circuits operate and how the brain functions overall.
“This product is a testament to the power of this unprecedented, cross-cutting collaboration and paves our path for more precision brain treatments,” said Dr. John Ngai, director of the NIH BRAIN Initiative.
“This work is helping us establish a baseline understanding of what the brain is like at the cellular level,” Professor Ren said.
“This will make it possible to draw comparisons between our baseline and brains with neurological and psychiatric disorders.”
“Studying the brain this way could help us discover new therapeutic approaches for these conditions.”
“Humans have evolved over millions of years, and much of that evolutionary history is shared with other animals,” said Professor Joseph Ecker, a researcher at the Salk Institute for Biological Studies.
“Data from humans alone is never going to be enough to tell us everything we want to know about how the brain works.”
“By filling in these gaps with other mammalian species, we can continue to answer those questions and improve the machine-learning models we use by providing them more data.”
“The brain isn’t homogenous, and diseases don’t affect all parts of the brain equally,” Professor Ren said.
“Insights from this research and the BRAIN initiative as a whole are helping us better understand what types of cells are affected in specific diseases.”
“We hope this will pave the way for more precise, targeted therapies that can heal diseased cells without affecting the rest of the brain.”
The results appear in ten papers in the journal Nature.
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