Lawrence and her research team devised a method to simulate the natural process of silencing an X chromosome in all female mammals. Both X chromosomes contain a gene called XIST. When XIST is activated, it generates an RNA molecule, which will cover the surface of the chromosome like a blanket to prevent the expression of other genes. In female mammals, activation of a copy of the XIST gene causes silence of the X chromosome where it is located.
The Lawrence research team integrated the XIST gene into a chromosome 21 in the cells of patients with Down syndrome. The research team also inserted a genetic "switch", which enabled them to turn on XIST by giving cells doxycycline quantitatively. Doing so inhibits the expression of individual genes on the extra pathogenic chromosome 21.
The experiment used induced pluripotent stem cells, and the researchers hope that one day they will be able to study the effects of Down syndrome in different organs and tissue types. This research work will enable new treatments to deal with the degenerative symptoms of Down syndrome, for example, patients with Down syndrome have a tendency to form early dementia.
Nissim Benvenisty, a stem cell researcher at the Hebrew University, said: "The idea of â€‹â€‹turning off the entire chromosome in Down syndrome research is very interesting." He expects that in future research, the researchers will divide the cells into two groups, one group. The extra chromosome 21 in the middle is turned on, and another set of extra chromosome 21 is turned off to compare their functional mechanisms and response to treatment.
Researchers have previously used different types of genetic modification to remove extra chromosomes in the cells of Down syndrome patients. The technology is based on the fact that induced pluripotent stem cells that carry three copies of chromosome 21 sometimes sometimes kick extra chromosomes out. "But the headache is that you can't control it," said Mitchell Weiss, a stem cell researcher at the Children's Hospital of Philadelphia, Pennsylvania.
However, Weiss said that most methods also have their own flaws: turning on XIST may not block all gene expression on extra chromosomes, which may lead to confusion in the experimental results.
However, Weiss still believes that this method can provide new treatment for Down syndrome and can be used to study other chromosomal diseases, such as Patau syndrome caused by trisomy 13 chromosome.
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