Biomedical data scientists at the Stanford University School of Medicine have shown that the number of genes a cell uses to make RNA is a reliable indicator of how developed the cell is, a finding that could make it easier to target cancer-causing genes.
Cells that initiate cancer are thought to be stem cells, which are hard-to-find cells that can reproduce themselves and develop, or differentiate, into more specialized tissue, such as skin or muscle -- or, when they go bad, into cancer.
Right now, targeted therapies are focused on specific genes or molecules, the vast majority of which may not be specific to cancer stem cells. 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." Aaron Newman, PhD, assistant professor of biomedical data science and a member of the Institute for Stem Cell Biology and Regenerative Medicine
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.
What the scientists showed is that as stem cells become more differentiated and more like adult cells, they express fewer and fewer genes. Previously, other researchers had noticed this correlation and thought it might be an interesting coincidence. But Newman and his colleagues were the first to sort through thousands of single-cell genetic tests in public databases and prove this pattern was consistent and reliable.
Newman and MD-PhD student Gunsagar Gulati combined the measurement of the number of genes expressed in a cell with the measurement of the number of RNA copies created per gene as the basis for a computer algorithm, CytoTRACE, designed to determine how developmentally advanced cells are.
A paper describing the research is being published online Jan. 24 in Science . Newman is the senior author. Gulati and Shaheen Sikandar, PhD, an instructor at the institute, share lead authorship. Tumor cells are diverse
Cancerous tumors can contain many millions of cells, each of which may have thousands of gene mutations. The cells in a tumor are diverse. Most will be differentiated cells that die out naturally on their own, while relatively few are the more dangerous cancer stem cells, or tumor-initiating cells. These cells are hard to find and therefore hard to characterize using current methods, but far easier to find with CytoTRACE.
"As a cancer researcher, what I find most exciting is that this tool helps us find the tumor-initiating cells that have long been known to be responsible for resistance to treatment, metastasis and relapse after treatment," Sikandar said.
Michael Clarke, MD, one of the authors of the paper, was the first researcher to identify cancer stem cells in a solid tumor. A professor of medicine at Stanford, Clarke said that CytoTRACE, which analyzes data on all the RNA created in a single cell, can quickly recapitulate research that takes years using traditional methods. "The way that we currently find cell markers for cancer stem cells is to make educated guesses about which markers will likely be important, then sort those cells and look for stem cell activity," said Clarke, the Karel H. and Avice N. Beekhuis Professor in Cancer Biology and associate director of the Institute for Stem Cell Biology and Regenerative Medicine. Related Stories
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