Researchers at the Babraham Institute have revealed a new knowledge of the molecular switches that control gene activity within human embryonic stem cells. This insight provides brand new avenues for improving the efficiency of being able to generate stem cells to create a desired cell type — an important requirement to fulfil their promise in regenerative medication.

In the developing embryo plus during the specialisation of stem cells, the activity of genetics must be tightly controlled (by a process called epigenetics) so the correct genes are switched on and off at the correct time and in the right cells. One of the main ways that this process will be regulated is by a protein complex called Polycomb Repressive Complex 2 (PRC2), which keeps genes switched off until they may be needed. We know from previous studies that PRC2 is essential for controlling gene activity during the development of the fruit take flight and the mouse, but we know very little about its function in human development or in the specialisation of come cells.

As described in the journal Cellular Reports, the researchers used the CRISPR gene editing way to delete PRC2 from human embryonic stem cells. Lack of PRC2 caused the cells to switch on many genes which are not normally active in these cells. Interestingly, the group of genes that were switched on have important roles in the development of specialised cell types in the developing embryo. This particular exciting finding reveals that one of the main functions associated with PRC2 is to keep these identity-specifying genes switched off throughout the very early stages of human development until they are necessary. The researchers also discovered that the quality and stability from the embryonic stem cells were compromised when the set of genetics was aberrantly switched on. These changes led to the inability associated with embryonic stem cells lacking PRC2 to specialise properly into mature cell types.

Dr Philip Rugg-Gunn, senior author on the research paper and study group leader at the Babraham Institute explained: “This function is exciting because it reveals that gene activity is certainly controlled by similar molecular switches in human growth as in other species such as the fly and mouse. We now have also uncovered human-specific differences in the way that embryonic originate cells respond to genes being misregulated. These findings offer new insights into the development of our own species, and may enable new ways to turn embryonic stem cells directly into useful cell types, such as heart and pancreas, which may be used for cell-replacement therapies. ”

This study was funded through grants provided to Dr Philip Rugg-Gunn by the Wellcome Trust and the Medical Research Authorities (MRC). The Babraham Institute is strategically funded with the Biotechnology and Biological Sciences Research Council (BBSRC).

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