For the first time, scientists have been able to develop male and female near-identical human induced pluripotent stem cells (hiPSCs) from the same person.
hiPSCs are a valuable biological tool. These are cells that can be reprogrammed to return to a stem cell-like state. They are used for therapeutics, and molecular investigations of diseases and cellular behavior. However, it can be difficult to determine sex differences in hiPSCs, which is important as the different sexes can experience different disease incidence rates, medication responses, and symptoms.
In humans (and yes, it does differ depending on the organism) biological sex is determined by the sex chromosomes. In females, there are two X chromosomes (XX); in males, one X and one Y chromosome (XY). However, some conditions cause the sex chromosome ratios to differ from the typical.
Klinefelter syndrome is a genetic condition that causes a person to have two X chromosomes and one Y chromosome (XXY). In this new study, the researchers created stem cells from the white blood stem cells of a donor with this syndrome. The donor in this case had an interesting mosaic phenotype, where they had a large number of both XXY and XY cells. The unusual phenotype allowed the researchers to create stem cells that contained the same DNA, but with different sex chromosome complements: 46XX, 46XY, 45X0, and 47XXY hiPSCs.
These stem cell lines have created a simple model for scientists that allow research teams to compare how different cells can respond to medicines, or to model illnesses. Any differences observed would probably be due to genetic sex, allowing scientists to differentiate between hormonal and chromosomal differences. Previous studies had to conduct their research on large cohorts or using multiple cell lines, which can introduce a lot of noise to the data.
The researchers in the study did multiple experiments and found that they replicated findings from previous studies with other models. This is encouraging news, and confirmed that these stem cells can confirm previously reported differences due to the sex chromosomes.
The team were also able to change the stem cells into immature neurons, and confirmed previous findings of early neural development sex differences.
The future is bright for this research, and the team will continue investigations into early development. There are many applications for these cells in lots of areas of science, including therapeutics. Currently, there is the limitation associated with using cells from just one person, but as the research expands, more lines from more genetic backgrounds can be created.
This work was published in Stem Cell Reports.