A new study has identified key molecular switches that improve the efficiency of being able to drive embryonic stem cells to become a desired cell type; essential for their use in regenerative medicine.
Researchers from the Babraham Institute (Cambridge, UK) have explored the role of the PRC2 protein and how it regulates gene activity in human development. The study, published in Cell Reports, utilized a gene editing technique to reveal the main function of PRC2 in switching off identity-specifying genes, meaning it could play a role in stem cell specialization.
Scientists lead by Peter Rugg-Gunn (Babraham Institute) utilized the CRISPR gene editing technique to remove PRC2 from human embryonic stem cells. The lack of PRC2 caused cells to switch on many genes that were not normally active; genes that have vital roles in specialized cell type formation.
The results demonstrated that PRC2 functions to keep identity-specifying genes switched off in the early stages of human development, until they are required. When switching on the set of genes aberrantly, scientists observed that the stability and quality of the embryonic stem cells were compromised; this lead to the embryonic stems cells, lacking PRC2, being unable to specialize into mature cell types.
This research confirms that PRC2 is necessary for controlling gene activity in human development as well as in other previously researched species: “This work is exciting because it reveals that gene activity is controlled by similar molecular switches in human development as in other species such as the fly and mouse. We have also uncovered human-specific differences in the way that embryonic stem cells respond to genes being misregulated. These findings provide new insights into the development of our own species, and might enable new ways to turn embryonic stem cells into useful cell types, such as heart and pancreas, which can be used for cell-replacement therapies,” commented Rugg-Gunn.
Sources: Collinson A, Collier AJ, Morgan NP et al. Deletion of the polycomb-group protein EZH2 leads to compromised self-renewal and differentiation defects in human embryonic stem cells. Cell Reports 17(10), 2700—2714 (2016); www.babraham.ac.uk/news/2016/12/controlling-gene-activity-in-human-development