Cambridge stem cell scientists have revealed new insight into sex chromosome changes in embryos that fundamentally alters the way we think about male and female early development.
In research published in the journal Cell Stem Cell, the scientists showed for the first time that a process called ‘X Chromosome Inactivation’ occurs transiently on male X chromosome, rather than just in females as previously thought.
X Chromosome Inactivation is an essential developmental process that ensures individuals receive the correct amount of genetic information for normal cell functions to occur. In males, who carry one X and one Y chromosome (XY), this genetic dosage is naturally delivered. In females, who carry two X chromosomes (XX), the correct genetic dosage is obtained through silencing of one of their X chromosomes via X Chromosome Inactivation.
The University of Cambridge research team, led by Dr José Silva from the Wellcome - MRC Cambridge Stem Cell Institute, used mouse embryonic stem cells to reveal that X Chromosome Inactivation starts on all X chromosomes regardless of sex (XX or XY). The cells halt the process in males and allow the inactivation to continue on one of the two X chromosomes in females.
“Our study shows that initiation of X chromosome inactivation occurs before the cell realizes whether it is male or female” explains Dr Elsa Sousa, who led the current research. “We previously thought that cells realised their sex by counting their X chromosomes prior to the initiation of X chromosome inactivation if female. Our research changes this paradigm. We now know we need to look earlier in the process to better understand the mechanisms driving sex-specific development.”
“This finding fundamentally changes how we think about embryonic development” adds Dr José Silva. “The new understanding that male cells undergo X chromosome inactivation allows us to study the process from a new perspective which we hope will serve as a springboard for future discoveries in the field”.
Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males, Elsa J. Sousa, Hannah T. Stuart, Lawrence E. Bates, Mohammadmersad Ghorbani, Jennifer Nichols, Sabine Dietmann, José C.R. Silva is published in Cell Stem Cell.
Dr Silva and Dr Sousa are part of the Department of Biochemistry at the University of Cambridge and are based at the Wellcome - MRC Cambridge Stem Cell Institute. The support of Wellcome, the Portuguese Foundation for Science and Technology and the Medical Research Council is gratefully acknowledged by José and the team.