Updated Brain Cell Map Connects Various Brain Diseases to Specific Cell Types
11/12/2017
Researchers have developed new single-cell sequencing methods that could be used to map the cell origins of various brain disorders, including Alzheimer’s, Parkinson’s, schizophrenia and bipolar disorder.
By analyzing individual nuclei of cells from adult human brains, researchers at the University of California San Diego, Harvard Medical School and Sanford Burnham Prebys Medical Discovery Institute have identified 35 different subtypes of neurons and glial cells and discovered which of these subtypes are most susceptible to common risk factors for different brain diseases.
“There are multiple theories regarding the roots of various brain diseases. Our findings enable us to narrow down and rank which types of cells in the brain carry the most genetic risk for developing these diseases, which can help drug developers pick better targets in the future,” said Kun Zhang, a professor of bioengineering at the UC San Diego Jacobs School of Engineering and co-senior author of the study.
This work builds off of a previous study published in Science, which Zhang also co-led, in which researchers identified 16 subtypes of neurons in the cerebral cortex. That study was the first large-scale mapping of gene activity in the human brain and provided a basis for understanding the diversity of individual brain cells.
“Our ultimate goal is to produce a complete cell atlas of the human brain,” Zhang said. “Here, we’ve created a fuller and more detailed map than what we’ve done in our previous work.”
In the new study, researchers developed a new generation of single-cell sequencing methods that enabled them to identify additional neuronal subtypes in the cerebral cortex as well as the cerebellum, and even further divide previously identified neuronal subtypes into different classes. The new methods also enabled researchers to identify different subtypes of glial cells, which wasn’t possible in the previous study due to the smaller size of glial cells.
The advance was made possible by combining next-generation RNA sequencing with chromatin mapping–mapping of DNA and proteins in the nucleus that combine to form chromosomes–for more than 60,000 individual neurons and glial cells. The work was published Dec. 11 in Nature Biotechnology.