Embryonic stem cells can, by definition, mature into any cell type in the body. They are able to maintain this state of so-called pluripotency with the help of a gene called Sox2. And now, researchers at the University of Toronto (U of T) have discovered the unseen force that controls it. These findings, reported in the latest issue of Genes & Development, offer much-needed understanding of the steps a cell must take as it grows up.
Led by U of T Professor Jennifer Mitchell, the research team were, for the first time, able to identify the specific molecular regulator that switched the Sox2 gene on and off at specific times during an embryonic cell’s lifetime. As Mitchell explained:
“We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells. Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell.”
The team named this region the Sox2 control region, or SCR.
For the last decade scientists have been using knowledge gleaned from the Human Genome Project to map how and when genes are switched on and off. Interestingly, the regions that control the gene in question aren’t always located close by.
This was the case with Sox2, said Mitchell. Early on, researchers had argued that Sox2 was regulated from nearby. But in this study, the team found the SCR, which controls Sox2, to be located more than 100,000 DNA base pairs away. According to Mitchell, the process by which the SCR activates Sox2 is fascinating:
“To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells… It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells.”
Indeed, despite a flurry of research breakthroughs and a promising number of clinical trials moving forward, there are still some fundamental aspects of stem cell biology that remain unknown. This discovery, argues Mitchell, is an important step towards reaching toward improving the way in which scientists manipulate stem cells to treat disease.