An international team of scientists from Belgium and the United States are studying revealing previously unknown details of the reprogramming of adult cells into induced pluripotent stem cells (iPSCs). They found that female and male cells behave differently after being reprogrammed into stem cells, and this is due to a different number of X chromosomes. The results of the work were published on April 19, 2018 in Stem Cell Reports.
Thanks to a promising technique known as cell reprogramming, it is possible to create stem cells from the patient’s skin cells, which will be used, for example, to restore vision in the future. Such cells, known as induced pluripotent stem cells or iPSCs, embryonic stem cells-like cells, can be turned into almost any specialized cell type of the human body.
IPSC have a lot of advantages compared with other methods of regenerative medicine. Firstly, embryos are not used for their production. And secondly, the reprogrammed cells are identical to the cells of the patient, so the body will be less likely to reject them.
“Cell reprogramming is revolutionising medicine, yet surprisingly little is known about how it actually works”, – says stem cell expert Vincent Pasque, assistant professor at KU Leuven, Belgium, one of the leading authors of the work.
Together with Kathrin Plath from UCLA, Vincent Pasque led a study of the process of reprogramming mature cells in iPSCs. For this, the scientists divided the cells into received from men and from women. The researchers found that the cells behave differently after the reprogramming process because of a different number of X chromosomes – in female cells there are two of them, and in males – one.
Vincent Pasque explains: “In a normal situation, one of the two X chromosomes in female cells is inactive. But when these cells are reprogrammed into iPS cells, the inactive X becomes active. So the female iPS cells now have two active X chromosomes, while males have only one.
We now know that this explains the different behaviour of male and female cells after reprogramming because, over time, female cells lose one of the two X chromosomes and start behaving more or less like male iPS cells.”
Differences between male and female iPSCs are most noticeable for one of the key processes in the field of epigenetics – DNA methylation, a alteration that changes the activity of the DNA segment without changing its sequence. The investigators found that DNA methylation disappears in female iPSC, but remains unchanged in males.
“Our study also indicates that the path towards iPS cells involves the use of specific control switches on DNA called enhancers”, – adds Dr. Constantinos Chronis from UCLA.
“Our results show that studying male and female cells separately is key to a better understanding of how iPS cells are made. And we really need to understand the process if we want to create better disease models and to help the millions of patients waiting for more effective treatments”, – concludes Vincent Pasque.