Detailed cell maps of the human brain bring new treatment possibilities 

Yang Eric Li, PhD

In Yang Eric Li’s newly published paper in Science, A comparative atlas of single-cell chromatin accessibility in the human brain, he and his colleagues revealed the largest maps of the human brain, uncovering new information that was never available before. 

“For this research, we profiled chromatin accessibility from 1.1 million brain cells, and identified 107 distinct cell types.” says Yang Eric Li, Assistant Professor of Genetics and Neurosurgery. “Switches turn lights on or off. The regulatory element is like the switch that controls the on and off of the gene.” This work delineated more than a half million candidate cis-regulatory elements involved in gene regulation in one or more cell types, 47% of which are novel.

Li’s paper is one of the 21 papers published as a package across ScienceScience Advances, and Science Translational Medicine on October 13, 2023. The research is a component of the BRAIN Initiative , an ongoing project launched a decade ago by President Obama.  It is primarily funded by the National Institute of Health with the goal of compiling a comprehensive inventory of various brain cell types.

A major impact of this research is the great opportunity it provides to examine relevant cell types associated with common neuropsychiatric disorders, which will accelerate the development of new strategies for treating these disorders.

Yang Eric Li, PhD

“Scientists already know that hundreds of tiny variants in our DNA can lead to Alzheimer’s, Autism, major depression, schizophrenia and many other neuropsychiatric disorders.” says Dr. Li, “Now we know schizophrenia is more associated with excitatory neurons, and a type of cell we call microglia is relevant to Alzheimer’s disease.”

One of the biggest challenges for this research is computational. Clustering millions of cells has not been done before, most of the algorithms or standard approach wouldn’t work on datasets at such a large scale. Li and his colleagues had to figure out a way to build up computational pipelines for large-scale data integration. “Interpreting the function of subtle changes in our DNA is another challenging part. There is no way to tell the function by staring at the altered DNA sequence” says Dr. Li. Thus cutting edge AI models were developed by Dr. Li to understand precisely how risk variants in our genome affect the function of individual brain cells.

A research published by the World Health Organization (WHO) estimated that 1 in 8 people will suffer at least one kind of mental disorder. And mental disorder is the Top 1 burden of disease in the United States. While a big issue to human health, we still don’t know enough about the human brain to determine treatments for certain diseases, this is what prompted Li to devote his research to mental disorders and brain tumors that would affect his family and many others.

Prior to joining Washington University in St. Louis, Li worked in Dr. Bing Ren’s Gene Regulation Laboratory at University of California San Diego as a postdoctoral researcher. Dr. Li’s research focuses on developing computational tools and using advanced (epi)genomic techniques to understand gene dysregulation in brain tumors and neuropsychiatric disorders. His newly established lab will be located in the new Neuroscience Building and he is currently recruiting students, postdocs at all levels. Find out more information about his lab here