Scientists from the University of California San Diego School of Medicine have made significant progress in understanding the complexity of the human brain. Despite all our cells sharing the same DNA, there are thousands of different cell types in the brain, each with its own unique structure and function. The challenge for neuroscientists has been to determine how genes are switched on and off to form this diverse array of cell types.
In two groundbreaking studies recently published in the journal Nature, the researchers have made great strides in unraveling this mystery. They analyzed over 2.3 million individual brain cells from mice to create a comprehensive map of the mouse brain. By using artificial intelligence, they were able to predict which stretches of DNA determine a specific brain cell’s type. Additionally, they studied the brains of humans and primates to investigate the evolutionary processes that govern gene expression in cells.
Professor Bing Ren, senior author of the studies, likens a cell’s DNA to its language. Just as there are root words shared across different languages, certain genes and gene expression patterns are conserved across different species. Understanding and interpreting the brain’s molecular language, according to Ren, can provide valuable insights into the workings of the brain and how neuropsychiatric conditions develop.
The two new research papers are part of a larger effort to create the first complete cell type atlas of a mammalian brain. Led by researchers from UC San Diego, the Salk Institute for Biological Studies, and the Allen Institute for Brain Science, this ambitious project is supported by the National Institutes of Health’s BRAIN Initiative. The initiative, launched in 2014, aims to deepen our understanding of the human mind and revolutionize the treatment and prevention of brain disorders.
Ren emphasizes the importance of establishing a baseline understanding of brain cells. By comparing this baseline to the brains of individuals with neurological and psychiatric disorders, researchers can uncover new therapeutic approaches. The ultimate goal is to develop targeted therapies that can heal diseased cells without affecting the rest of the brain.
Collaboration across species is key to this research. While humans have unique characteristics, we share a considerable amount of evolutionary history with other animals. By studying the brains of other mammals alongside humans, scientists can fill in the gaps in their knowledge and improve their machine learning models. The researchers found that cell-type-specific gene expression patterns evolve rapidly compared to patterns shared across cell types. This insight could explain why there are so many different cell types in the brain.
The studies have already revealed relevant insights into human diseases. Many of the genetic programs that determine cell type are located in parts of the genome that have been implicated in various human diseases, such as multiple sclerosis, anorexia nervosa, and tobacco use disorder. This discovery has the potential to shed light on how these neuropsychiatric disorders impact the brain.
The researchers’ efforts align with the BRAIN Initiative’s Cell Census Network (BICNN), which aims to classify human brain cells into more precise subtypes and track how cellular features change over time. Earlier this year, Ren and other scientists published an atlas of the human brain, identifying over a hundred different types of brain cells. The newly created atlas of the mouse brain complements this work and expands upon it by comparing brains across different species.
In conclusion, the recent studies conducted by UC San Diego researchers shed light on the complex mosaic of cell types within the brain. By mapping the mouse brain and utilizing artificial intelligence, scientists are getting closer to understanding how genes determine a cell’s type and function. The insights gained from this research have the potential to revolutionize our understanding of brain disorders and lay the groundwork for more targeted therapies in the future.
