London, UK – Our biological history can be traced back to a small group of cells called embryonic stem cells, which through cell division, give rise to cells that specialise to perform a specific role in the body – a process known as differentiation.
As part of the research, published in Cell Stem Cell, Crick scientists found that embryonic stem cells differentiate unexpectedly early, irreversibly committing to become each of the more than 200 cell types in the body.
They showed this was as a result of a newly identified small group of genes becoming activated, which they named ‘early-commitment genes’.
“Working with stem cells and mathematical models, we’ve identified a new class of genes which are responsible for regulating one of the earliest stages of human development,” says Silvia Santos, author and group leader in the Quantitative Cell Biology Laboratory at the Crick.
"Once these genes are activated, it’s a question of minutes before the cells fully commit to differentiation. The speed of this is incredibly surprising, especially if you consider how the first signs of differentiation, that’s the embryo developing the first embryonic germ layers, take about three days. These layers ultimately give rise to all the tissues in the growing foetus weeks later.”
A special job for the GATA3 gene
The researchers focused on one early-commitment gene, called GATA3. When this gene was activated experimentally in the lab, embryonic stem cells quickly committed to differentiation. On the other hand, when this gene was deleted, this process was sluggish and not quite right.
“GATA3 is crucial to the healthy, timely differentiation of stem cells. Once it’s switched on, this gene triggers a positive feedback loop, which helps it stay active. In turn, this ensures that the cells remain differentiated, and do not reverse back to a stem cell state,” says Alexandra Gunne-Braden, co-lead author and postdoc in the Quantitative Cell Biology Laboratory at the Crick.
This research used stem cells taken from embryos donated by people undergoing IVF. The donated embryos were not needed in the course of their fertility treatment and would have otherwise been destroyed.
“When embryonic stem cells commit to specialisation is a fundamental and yet until now, unanswered question,” continues Silvia Santos.
“It’s important we understand more about this, as the healthy function of cells is underpinned by the process of how cells acquire and remember their identity during the process of differentiation. This valuable insight into early human development could open up new avenues for research into diseases that occur when this process goes wrong.”
NOTES TO EDITORS
Full Study: Alexandra Gunne-Braden ,Adrienne Sullivan, Borzo Gharib,i Rahuman S.M. Sheriff, Alok Maity, Yi-Fang Wang, Amelia Edwards, Ming Jiang, Michael Howell, Robert Goldstone, Roy Wollman, Philip East Silvia & D.M. Santos (2020) ""target="_blank">GATA3 Mediates a Fast, Irreversible Commitment to BMP4-Driven Differentiation in Human Embryonic Stem Cells, Cell Stem Cell, published online 16 Apr 2020 (DOI: 10.1016/j.stem.2020.03.005).
Media contact: Alice Deeley, Francis Crick Institute (+44 020-379-65360 or email@example.com)