For the first time, Researchers have achieved a groundbreaking achievement by creating the first complete cell atlas of a mammalian brain, specifically a mouse. This complete map details over 32 million cells, their types, locations, molecular information, and connectivity.
The atlas provides an in-depth look at the mouse brain, which is an important model in neuroscience, and sets the framework for enhanced treatments for mental and neurological problems. It includes structural, transcriptomic, and epigenetic information, and it serves as an outline for brain circuit operations and functioning.
The findings were funded by the National Institutes of Health’s Brain Research and appear in a collection of 10 papers published in Nature.
Joshua A. Gordon, (M.D., Ph.D., Director of the National Institute of Mental Health, part of the National Institutes of Health) said “The mouse atlas has brought the complex network of mammalian brain cells into unparalleled focus, giving researchers the details needed to understand human brain function and diseases.”
The types of cells and how they are arranged inside the various mouse brain areas are described in the cell atlas. The transcriptome, or the entire collection of gene readouts in a cell that encodes instructions, is described in great detail in the cell atlas in addition to this structural information for making proteins and other cellular products.
The transcriptomic information included in the atlas is progressively organized, detailing cell classes, subclasses, and thousands of individual cell groups within the brain.
The atlas also describes the cell epigenome—chemical changes to a cell’s DNA and chromosomes that change how 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 unparalleled map of cellular organization and diversity across the mouse brain.
The atlas also lists the neurotransmitters and neuropeptides used by distinct cells, as well as the relationships between cell types inside the brain. This data can be utilized to create a thorough roadmap for how chemical signals are triggered and transmitted in various areas of the brain.
Those electrical signals are the basis for how brain circuits operate and how the brain functions overall.
John Ngai, (Ph.D., Director of the NIH BRAIN Initiative) said “This product is a testament to the power of this unparalleled, cross-cutting collaboration and paves our path for more precision brain treatments”.
The core aim of the BICCN, a groundbreaking, cross-collaborative effort to understand the brain’s cellular makeup, is to develop a comprehensive inventory of the cells in the brain—where they are, how they develop, how they work together, and how they regulate their activity—to better understand how brain disorders develop, progress, and are best treated.
Dr. Ngai said, “By leveraging the unique nature of its multi-disciplinary and international collaboration, the BICCN was able to accomplish what no other team of scientists has been able to before”.
“Now we are ready to take the next big step—completing the cell maps of the human brain and the nonhuman primate brain.”
The BRAIN Initiative Cell Atlas Network (BICAN) is the next stage in the NIH BRAIN Initiative’s effort to understand the cell and cellular functions of the mammalian brain. BICAN is a transformative project that, together with two other large-scale projects—the BRAIN Initiative Connectivity Across Scales and the resources for Precision Brain Cell Access—aim to revolutionize neuroscience research by illuminating foundational principles governing the circuit basis of behavior and informing new approaches to treating human brain disorders.
In addition to this, an online platform, Allen Brain Cell Atlas, has been presented to visualize the mouse whole-brain cell-type atlas along with the single-cell RNA-sequencing and MERFISH datasets.
The researchers systematically analyzed the neuronal and non-neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and geographical specificity for each cell type.
The results reveal unique features of cell-type organization in different brain regions—in particular, a division between the dorsal and ventral parts of the brain. The dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other.
The study also uncovered extraordinary diversity and variety in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types.
Finally, the researchers found that transcription factors are major determinants of cell-type classification and identified a combinatorial transcription factor code that defines cell types across all parts of the brain.
The whole mouse brain transcriptomic and spatial cell-type atlas establishes a benchmark reference atlas and a foundational resource for integrative investigations of cellular and circuit function, development, and evolution of the mammalian brain.
In conclusion, the creation of the complete cell atlas of the mammalian brain, particularly the mouse brain, represents a significant leap forward in our understanding of brain function and disorders. This complex map provides a detailed insight into the cellular organization and diversity across the brain, paving the way for the development of precision for mental and neurological disorders. The research not only sheds light on the intricate network of mammalian brain cells but also sets the stage for further advancements in neuroscience research and the treatment of brain disorders.
