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A historic neuroscience milestone has been achieved by researchers affiliated with the National Institutes of Health's (NIH) Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative Cell Census Network (BICCN) initiative with the recent publication of an atlas of brain cells associated with mammalian movement in the journal Nature, representing the cumulation of nearly half a decade of progress.
Understanding the structure and function of the brain can accelerate the discovery of novel ways to treat brain diseases and neurological conditions such as addiction, depression, anxiety, autism spectrum disorder, ALS (Lou Gehrig’s disease), schizophrenia, Alzheimer’s disease, epilepsy, dementia, Parkinson’s disease, and many more.
The work represents a collaboration of more than 250 scientists in three continents affiliated with over 45 institutions including The Salk Institute for Biological Studies, the Allen Institute for Brain Science, the University of California San Diego (UCSD) School of Medicine, Harvard University, Sanford Burnham Prebys Medical Discovery Institute, the Massachusetts Institute of Technology (MIT), the University of California Berkeley (UC Berkeley), the University of California Los Angeles (UCLA), the Broad Institute of MIT and Harvard, the University of California San Francisco (UCSF), the Johns Hopkins School of Medicine, and many other leading institutions. The collaboration resulted in over seventeen papers published in Nature.
The researchers combined integrated computational analysis with data from single-cell transcriptomes, chromatin accessibility, DNA methylomes, morphology, electrophysiological properties, and input–output mapping.
Transcriptomics is the study of the transcriptome—all of the RNA molecules inside a cell. To construct the atlas, the researchers applied single-cell RNA sequencing (scRNA-seq) to the neocortex and other brain areas to understand the hierarchical organization of transcriptomic cell types.
By combining epigenomic and single-cell transcriptomic analysis, the researchers were able to see a unified molecular genetic landscape of cortical cell types that combine the chromatin state, DNA methylation, and gene expression.
Epigenomics is the study of how the environment can change how your genes function. Changes to the genome and the epigenome can cause cancer. Lifestyle, behavior, and environment can change the epigenome. For example, cigarette smoking increases the risk of many diseases such as cancers of the lung, liver, and colon, as well as both respiratory and cardiovascular diseases. For certain cancers, changes in the epigenome switch off the genes that regulate cell growth, resulting in uncontrolled growth, or hinder the ability for the immune response to fight tumors.
Chromatin is the DNA and protein found inside a chromosome in eukaryotic cells. Most of the proteins in chromatins are histones. Unlike prokaryotes, eukaryotes are organisms that have cells with a nucleus that is surrounded by a membrane.
DNA methylation, an epigenetic mechanism, is a biological process that regulates gene expression by adding a methyl (CH3) group to DNA, which often changes the way genes express and function.
Gene expression refers to the process by which the information from a gene, the genetic code, is used to produce molecules. Epigenetic changes can alter gene expression. The epigenome are chemical compounds and proteins that can attach to DNA to turn genes on or off, thereby controlling protein production in certain cells and change the way cells apply DNA instructions. Modifications to the epigenome can cause the genes for immune responses or cell growth to switch on or off.
The team of scientists performed an analysis across three species (mouse, marmoset and human) in order to classify transcriptomic types. This was accomplished by creating a consensus taxonomy to standardize mammalian cell types.
“Thanks to this groundbreaking collaboration, we now have a comprehensive understanding of the brain cells found in the motor cortex of the brain and their basic functional properties,” said Francis S. Collins, M.D., Ph.D., the Director of the National Institutes of Health in a statement. “The atlas will provide a springboard for future research into the structure and function of the brain within and across species.”
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