In mammals, lineage committed female cells display X chromosome inactivation, where one of the two X chromosomes becomes silent to equalise dosage with XY males. This is an extreme example of gene silencing, where hundreds of genes become silenced in parallel through epigenetic mechanisms. Pluripotent female stem cells do not display X chromosome inactivation and are instead in a pre-inactivated state, transcriptionally active from both X chromosomes. This makes female pluripotent stem cells unique, even from male stem cells, and there are associated functional differences. These differences may have profound consequences when male and female stem cells are utilised for regenerative medicine.
This project utilises molecular biology, genomics and microscopy to study epigenetic silencing and how this shapes female pluripotent stem cell identity.
The Blewitt lab studies how genes are turned on and off; a process called epigenetic gene regulation. The DNA of a fertilised egg contains all the information required to form an adult, with the vast array of different cell types determined by which genes are on and off in a given cell. Proteins called epigenetic modifiers turn different genes on and off throughout development, allowing differentiation from the fertilised egg through to an adult organism. Disease can occur if this process fails. Despite their importance, most human epigenetic modifiers likely remain unknown and the ones that we do know have undiscovered functions. Our lab is identifying potential new epigenetic modifiers and revealing their role in development and disease.