In the developing embryo and during the specialization 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
specialization of stem cells.
‘One of the main functions of Polycomb Repressive Complex 2 (PRC2) is to keep the embryonic stem cells switched off during the very early stages of human development until they are required.’
Researchers at the Babraham Institute have 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 fulfill their promise in
As described in the journal Cell Reports
, 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 specialized cell types in the developing embryo.
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
specialize correctly into mature cell types.
Dr. Peter Rugg-Gunn, senior author on the research paper and research
group leader at the Babraham Institute explained, "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