Scientists Created Male and Female Cells From a Single Person

An anonymous reader quotes a report from Scientific American: Most people have two sex chromosomes, either two X's or an X and a Y, which give rise to female or male biological attributes on a spectrum. Studies suggest these chromosomes also have much broader effects, contributing to processes that include immune system function, neuronal development, disease susceptibility and reactions to drugs. But scrutinizing the specific role of X and Y chromosomes is challenging. With current tools, it is difficult to disentangle the effects of genes versus hormones, for example. Now scientists have devised a tool that could overcome this obstacle -- by generating XX and XY cells from a single person for the first time. This unique set of cells could help researchers tackle long-standing questions about how sex chromosomes affect disease and the role they play in early development. Benjamin Reubinoff, a professor of obstetrics and gynecology at the Hadassah Medical Center in Israel, and his team began the project to overcome barriers facing investigations of sex differences in humans. Currently there are two major ones, according to Reubinoff: the difficulty of separating chromosomal and hormonal effects and the inability to pinpoint the effects of X and Y chromosomes while ruling out contributions from the rest of a person's genetic makeup. "The main reason for doing this study was the lack of a good model to study differences between males and females in humans," Reubinoff says. "There have been animal models, but a model in humans was not available." To create such a model, Reubinoff, his former M.D. and Ph.D. student Ithai Waldhorn and their colleagues first obtained white blood cells previously collected from a person with Klinefelter syndrome, a condition in which male individuals are born with an extra X chromosome. The cells came from the repositories of the Coriell Institute for Medical Research, where people donate samples for use in a wide range of biomedical research projects. The donor had a rare "mosaic" form of the condition, in which some of their cells had three sex chromosomes (XXY), some had two X chromosomes, and some had one X and one Y. The researchers reprogrammed all three cell types into induced pluripotent stem cells, which have the capacity to self-renew and to develop into neurons, muscle cells or other cell types. Ultimately the team generated XX and XY cells that -- apart from their sex chromosomes -- were genetically identical. The researchers then conducted a series of experiments replicating findings from prior studies with other models. For example, they confirmed previously reported differences in genes that were turned on in XX or XY cells. They also coaxed their stem cells to develop into immature versions of neurons and found evidence of previously reported sex differences in early neural development. "It was reassuring to see that the model really shows differences between the sexes that were reported from other systems," Reubinoff says. The findings were published last month in Stem Cell Reports. "This is a very well-designed study that validates the notion that sex differences start early in development -- and that they depend on the sex chromosomes because that's the only thing that can account for those differences," says Nora Engel, a professor of cancer and cell biology at Temple University.

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