JANUARY 29, 2020, New York— A study led by Aaron Newman of the Ludwig Center at Stanford shows that the number of genes a cell uses to make RNA is a reliable indicator of how developed the cell is, a finding that should be of great value to cancer drug development.
A relatively rare subset of cancer cells, known as cancer stem cells, are thought to initiate malignancies and drive metastasis. “Right now, targeted therapies are focused on specific genes or molecules, the vast majority of which may not be specific to cancer stem cells,” said Aaron Newman, a Ludwig investigator and assistant professor of biomedical data science and a member of the Institute for Stem Cell Biology and Regenerative Medicine at the Stanford University School of Medicine. “Usually these therapies don’t work for very long. But if you can identify the least-differentiated cells and then look for markers specific to them, it’s no longer a guessing game to find the genes to target.”
The study’s finding is also significant because identifying stem cells of various tissue types is an important step toward regenerating damaged or malfunctioning tissues.
A paper describing the research was published online Jan. 24 in Science.
Newman’s team show that as stem cells become more differentiated and more like adult cells, they express fewer and fewer genes. Other researchers have noticed this correlation, but Newman and his colleagues were the first to sort through thousands of single-cell genetic tests in public databases and prove the pattern consistent and reliable.
A combination of measurements—the number of genes expressed in a cell and the number of RNA copies created per gene—served as the basis for a computer algorithm, CytoTRACE, designed to determine how developmentally advanced cells are.
The researchers used CytoTRACE to query single-cell RNA data for triple-negative breast cancer, which is relatively dangerous because its growth doesn’t rely on the biochemical pathways that drugs usually target to treat breast cancer. Not only did CytoTRACE identify known markers of cancer stem cells, it also spotted a marker that had not been previously been thought to be important.
The Stanford Medicine release from which this summary is derived can be found here.