Scientists create male and female cells from one individual

By Sola Charles

Scientists have devised a tool that could generate 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 Centre 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. There have been animal models, but a model in humans was not available.”

To create such a model, Reubinoff, and 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 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. 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 story is published in Stem Cell Reports.