Writing in the journal PLOS Genetics, researchers from Michigan State University describe how they came across important clues about the origins of stem cells from examining critical early life stages of the mammalian embryo.
Image credit: G.L. Kohuth
There are two ways to make pluripotent stem cells – the “master” precursor cells that have the potential to become any cell of the body.
One way is when the embryo creates them in the first stages of life. Scientists describe this way as being so perfect that the embryo gets it right 100% of the time.
The other way to make pluripotent stem cells is the way scientists make them – by reprogramming mature cells so they return to an early stage of development.
Unfortunately, while this method promises to produce useful stem cells, at 1% success rate, it is currently much less efficient than the gold standard set by the embryo.
The Michigan State University (MSU) team hopes to close this gap and deliver a boost to regenerative medicine research. First author Amy Ralston, MSU assistant professor of biochemistry and molecular biology, says:
“Embryos have it figured out, and we need to learn how they’re doing it.”
The findings should also help fertility research, because the events Prof. Ralston and colleagues explored occur during the first few days of pregnancy, when most lost pregnancies fail.
The first discovery came when, working with mouse embryos, the team saw that a gene called Sox2 appeared to be active before any other genes known to play a role in stem cell formation.
The researchers are now trying to work out why Sox2 appears to be taking the leading role. Prof. Ralston explains:
“Now we know Sox2 is the first indicator that a cell is pluripotent. In fact, Sox2 may be the pre-pluripotent gene. We show that Sox2 is detectable in just one or two cells of the embryo earlier than previously thought, and earlier than other known stem cell genes.”
Image credit: MSU
One question they are addressing is, could this early Sox2 activity be what determines the source of stem cells in mammals?
The team also discovered that Sox2 does much more than previously thought. It appears to coordinate not only the activity of cells that make the fetus, but also of cells that establish the pregnancy, make the placenta and nurture the fetus.
So another question the team is focusing on is exactly why Sox2 plays this dual role. Prof. Ralston says they have already discovered a lot, but they want to dig deeper because:
“Reprogramming is amazing, but it’s inefficient. What we’ve learned from the embryo is how to improve efficiency, a process that could someday lead to generating stem cells for clinical purposes with a much higher success rate.”
The National Institutes of Health funded the study.
The study follows a recently publicized significant milestone in regenerative medicine, where stem cell researchers in Cambridge, UK, discovered how to successfully reset human pluripotent stem cells to the earliest developmental state.