Researchers have developed single-cell sequencing methods that can be used to map the cell origins of various brain disorders, such as Parkinson's, Alzheimer's, schizophrenia and bipolar disorder. The work was published yesterday in Nature Biotechnology and comes from researchers at the University of California San Diego, Harvard Medical School and the Sanford Burnham Prebys Medical Discovery Institute.
"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, co-senior author of the study.
In this study, using their newly developed single-cell sequencing techniques, researchers were able to identify neuronal subtypes in the cerebral cortex and cerebellum into different classes from brain data that was from adults between the ages of 20 to 50. They identified different subtypes of glial cells, which they couldn't do in their previous study.
To achieve this, the group combined next-generation RNA sequencing with chromatin mapping. Using this combined strategy, they mapped which cell types in the brain were affected by common risk alleles. They then ranked the subtypes of neurons or glial cells by genetic susceptibility.
"Now we can locate where the disease likely starts," Zhang said. "However, we are only mapping the genetic risk. We don't know the precise mechanism of how these specific cells actually trigger the disease."
The next step for the team is to expand their studies to other parts of the brain.