Scientists Unveil Complete Cell Map of a Whole Mammalian Brain

NIH-funded atlas characterizes more than 32 million cells in the mouse brain


Press release

For the first time, an international team of researchers has created a complete cellular atlas of an entire mammalian brain. This atlas serves as a map of the mouse brain, describing the type, location and molecular information of more than 32 million cells and providing information on the connectivity between these cells. The mouse is the most widely used vertebrate experimental model in neuroscience research, and this cellular map paves the way for a greater understanding of the human brain, arguably the most powerful computer in the world. The cell atlas also lays the foundation for the development of a new generation of precision therapies for people with mental and neurological brain disorders.

The findings were funded by the National Institutes of Health Brain research by advancing innovative neurotechnologiesInitiative ® or The BRAIN Initiative®, and appear in a collection of 10 articles published in Nature .

“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 disease,” said Joshua A. Gordon, MD, Ph. .D., director of the National Institute of Mental Health, part of the National Institutes of Health.

The cell 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, containing instructions for making proteins and other cellular products. The transcriptomic information included in the atlas is organized hierarchically and details classes and subclasses of cells and thousands of individual cell groups within the brain.

The atlas also characterizes the cellular epigenome (chemical modifications to a cell’s DNA and chromosomes that alter how the cell’s genetic information is expressed) and details thousands of epigenomic cell types and millions of candidate gene regulatory elements. different types of brain cells.

Together, the structural, transcriptomic, and epigenetic information included in this atlas provides an unprecedented map of cellular organization and diversity in the mouse brain. The atlas also provides an overview of the neurotransmitters and neuropeptides used by different cells and the relationship between cell types within the brain. This information can be used as a detailed model of how chemical signals are initiated and transmitted in different parts of the brain. Those electrical signals are the basis for how brain circuits work and how the brain functions in general.

“This product is a testament to the power of this unprecedented cross-functional collaboration and paves our path toward more precise brain treatments,” he said. John Ngai, Ph.D. Director of the NIH BRAIN Initiative.

Of the 10 studies included in this collection, seven are funded through the NIH BRAIN Initiative Cellular Census Network (BICCN) and two are financed through the largest NIH BRAIN Initiative . The primary goal of the BICCN, an innovative, cross-collaborative effort to understand the cellular composition of the brain, is to develop a comprehensive inventory of brain cells: where they are, how they develop, how they work together, and how they function. regulate their activity, to better understand how brain disorders develop, progress and are best treated.

“By leveraging the unique nature of their multidisciplinary and international collaboration, the BICCN was able to achieve what no other team of scientists had achieved before,” Dr. Ngai said. “Now we are ready to take the next big step: completing the cellular maps of the human brain and the brain of non-human primates.”

The BRAIN Initiative Cell Atlas Network (BICAN) is the next stage in the NIH BRAIN Initiative’s effort to understand cells and cellular functions in the mammalian brain. BICAN is a transformative project that, along with two other large-scale projects—the BRAIN Initiative Connectivity at All Scales and the Weaponry for precise access to brain cells —Aims to revolutionize neuroscience research by illuminating the fundamental principles governing the basic circuitry of behavior and informing new approaches to the treatment of human brain disorders.

Reference

Yao, Z., van Velthoven, CTJ, Kunst, M., Zhang, M., McMillen, D., Lee, C., Jung, W., Goldy, J., Abdelhak, A., Aitken, M., Baker, K., Baker, P., Barkan, E., Bertagnolli, D., Bhandiwad, A., Bielstein, C., Bishwakarma, P., Campos, J., Carey, D.,… Zeng, H. (2023). A high-resolution spatial and transcriptomic atlas of cell types throughout the mouse brain. Nature. https://www.nature.com/articles/s41586-023-06812-z

Subsidies

Projects funded through the NIH BRAIN Initiative

Spatial distribution of various cell types in the mouse brain. Here MERFISH was used to measure 500 genes in the mouse brain to reveal the complex distribution of cell types throughout the brain. Courtesy of Yao/van Velthoven/Zeng, Allen Institute.

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About the National Institute of Mental Health (NIMH): The mission of
NIMH
is to transform the understanding and treatment of mental illness through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

The NIH BRAIN Initiative is managed by 10 institutes whose missions and current research portfolios complement the goals of The BRAIN Initiative®: National Center for Complementary and Integrative Health, National Eye Institute, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, Institute National Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Drug Abuse, National Institute on Deafness and Other Communication Disorders, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and medical research. translational, and is investigating the causes, treatments and cures of common and rare diseases. For more information about NIH and its programs, visit the NIH website .

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