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Controlling gene activity in human development

last modified Jan 20, 2017 10:50 AM

06.12.16 - New research from Affiliate PI Peter Rugg-Gunn's Lab, published in Cell Reports, has revealed a new understanding of the molecular switches that control gene activity in human embryonic stem cells. This insight provides new avenues for improving the efficiency of being able to drive stem cells to create a desired cell type – an essential requirement to fulfil their promise in regenerative medicine.

In the developing embryo and during the specialisation of stem cells, the activity of genes must be tightly controlled (by a process called epigenetics) so that the correct genes are switched on and off at the right time and in the right cells. One of the main ways that this process is regulated is by a protein complex called Polycomb Repressive Complex 2 (PRC2), which keeps genes switched off until they are needed. We know from previous studies that PRC2 is necessary for controlling gene activity during the development of the fruit fly and the mouse, but we know very little about its role in human development or in the specialisation of stem cells.
 
The researchers used the CRISPR gene editing technique to delete PRC2 from human embryonic stem cells. Loss of PRC2 caused the cells to switch on many genes that are not normally active in these cells. Interestingly, the set of genes that were switched on have important roles in the formation of specialised cell types in the developing embryo. This exciting finding reveals that one of the main functions of PRC2 is to keep these identity-specifying genes switched off during the very early stages of human development until they are required. The researchers also discovered that the quality and stability of the embryonic stem cells were compromised when the set of genes was aberrantly switched on. These changes led to the inability of embryonic stem cells lacking PRC2 to specialise correctly into mature cell types.

Read more: Babraham Institute

Publication details:

Collinson A, Collier AJ, Morgan NP, Sienerth AR, Chandra T, Andrews S, Rugg-Gunn PJ. Deletion of the Polycomb-group protein EZH2 leads to compromised self-renewal and differentiation defects in human embryonic stem cellsCell Reports DOI: 10.1016/j.celrep.2016.11.032


138-2016-Rugg-Gunn

Immunofluorescent microscopy images of individual human embryonic stem cell colonies. Deletion of the Polycomb-group protein EZH2 in human embryonic stem cells leads to the loss of H3K27me3 signal (green). OCT4 expression in inset (red) indicates undifferentiated embryonic stem cells within the field of view.