Three investigators from the University of Tennessee Health Science Center are part of a team of scientists from around the country who developed a novel single-cell technology that could eventually lead to more targeted therapies for cancer.
Neil Hayes, MD, professor in the Division of Hematology and Oncology in the College of Medicine and director of the Center for Cancer Research, along with postdoctoral fellows from his lab, Hyo Young Choi, PhD, assistant professor, and Won-Young Choi, PhD, are among authors on the work done by a consortium that also included researchers from Stanford University, Harvard University, and the National Institutes of Health. The research is published in the prestigious journal Science.
“It is widely understood that DNA encodes the molecular instructions governing the function of all living beings,” Dr. Hayes explained. “DNA defines the differences between species, as well as the differences between individuals within a species.”
“We also understand that within all the more complex life forms, such as plants and animals, an individual is made up of many cells coming together to function as a single unit. If each of those cells contains a complete and identical copy of our DNA, then what rules govern why one cell is different from another? How do different cells read the same DNA, yet generate cells as different as those in our brains and bones?
The team’s research provides some answers.
In the study, the team examined samples from eight types of cancer using a novel technique called single-cell ATAC-seq, which identifies regions of the genome that are active in regulating genes.
“We were able to separate cancerous cells from other types of cells in tumors, like immune or connective tissue cells, to get a clearer picture of the specific abnormal gene regulation in cancer cells,” Dr. Hayes said. “We found that in cancer cells, chromatin (DNA and protein bundles) changes could reveal new insights into how different tumor subtypes behave, even within the same type of cancer. By using artificial intelligence, we were able to predict how specific genetic mutations affect chromatin accessibility, helping us understand how these mutations drive cancer.”
Dr. Hayes said this research represents a technical breakthrough in both the lab techniques and analysis techniques for assessing chromatin and gene expression at the single-cell level.
“This work provides a new tool for studying gene regulation in cancer and offers insights into how noncoding mutations—those not directly affecting protein production—can still play a significant role in driving cancer development,” he said. “Our findings could lead to more targeted therapies in the future.”