New Technology Demystifies Cell Activity to Help Explain Autoimmune Diseases Across Genders And Lifespan

Ines Martins, PhD avatar

by Ines Martins, PhD |

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Scientists at Stanford University School of Medicine have recently developed a groundbreaking technology that can help shed more light on the countless genetic molecules that can switch from active to inactive throughout an individual’s lifespan, much like switches. The study was titled, “Individuality and Variation of Personal Regulomes in Primary Human T Cells,” and is published in the journal, Cell Systems.

While most people are aware of the recessiveness and dominance of certain traits, such as when a red-haired mother and a black-haired father give birth to a red-haired daughter, in which case the red hair is a result of the dominant gene, some of our genes can switch on and off as we age. This phenomenon also occurs much differently in men and women, and can likely explain why some women are more predisposed to suddenly developing autoimmune diseases, such as scleroderma, rheumatoid arthritis, and lupus.

“Part of why this is possible is a new technology that was invented at Stanford for measuring the accessibility of the genome to regulatory elements,” explained the study’s senior author Howard Chang, MD, PhD, a professor of dermatology. Dubbed, ATAC-seq, this new technology allows scientists to study living cell activity in real time. “In the past,” he said, “people needed a huge number of cells to do this kind of measurement. You’d actually need a pound of flesh to get certain rare cell types. So you can’t get that out of a live person — and certainly not more than once, right?”

The creation of ATAC-seq began with a sample of lab-grown living cells from a dozen healthy participants. Chang clarified that these cells were obtained in vitro, meaning they are “copies of copies” and that it is likely they won’t exhibit the same cell behavior as what one would observe from original cells sampled from a live patient. These cells would not reflect the individual’s recent diet, stresses, or recent encounters with disease.

For this study, the researchers focused solely on observing T cell activity, which are relatively easy to isolate in a standard blood sample and play an important role in autoimmune diseases such as lupus. While lupus is commonly thought of as a B cell-driven disease, T cells are largely responsible for facilitating the production of autoantibodies by helping B cells differentiate, proliferate, and mature.

The researchers’ main objective was to complete a baseline study that shows how much of this gene-switching phenomenon occurs among healthy individuals, so that future investigations on cell activity in patients will have a basis of what is considered normal.

“We were interested in exploring the landscape of gene regulation directly from live people and look at differences,” said Chang. “We asked, ‘How different or similar are people?’ This is different from asking if they have the same genes.” Even in identical twins, he said, one twin could have an autoimmune disease and the other could be perfectly well. And, indeed, the team reported that over a third of the variation in gene activity was not connected to a genetic difference, suggesting a strong role for the environment. “I would say the majority of the difference is likely from a nongenetic source,” he added.