Scientists around the world hope to force embryonic stem cells to produce particular kinds of specialised cells, such as brain, muscle or pancreatic cells, on demand. The latest research, just published in the journal Developmental Cell, will have an important impact on efforts to control how embryonic stem cells behave, in order to use them for studying and treating disease.
The Paris and Edinburgh researchers used a novel variation on an established technique to study how cells behave as a mouse embryo develops. They were able to follow what happened to all of a single cell's offspring, and gained a new understanding of how tissues develop.
When a cell in the embryo divides, it faces a choice: It can make copies of itself, or produce more specialised ‘daughter' cells. If it makes specialised cells, it must decide what kind - the forerunners of skin, brain, skeleton? Whatever it decides, it can only produce two new cells. These next-generation cells then have to make a choice of their own. Gradually, a complex but very carefully controlled network of cells develops, connected by a sort of family tree.
Until now, biologists thought that embryonic stem cells first produce specialised groups of cells called germ layers. Each germ layer gives rise to a specific set of tissues of the body. The Paris and Edinburgh groups' research reveals a different picture, as Elena Tzouanacou of the Institut Pasteur explains:
'"Our results challenge the view that germ layers are major branch points in the ‘family tree' of cells in the developing embryo. Instead there are several, more staggered branches in the tree, not all connected to a single germ layer. These findings not only extend our knowledge of how tissues develop, but could also have an important impact on efforts to define strategies for growing pure populations of specific cell types in the lab."
The researchers have also identified a new kind of stem cell that generates a restricted set of tissues - spinal cord nerves, muscle and the skeleton. The newly discovered stem cells may prove very useful for producing pure samples of these cell types. While embryonic stem cells have enormous potential for medical applications, their ability to form a vast number of cell types makes them incredibly difficult to control. The more restricted capabilities of the new stem cells might make it easier to dictate how they behave.
Val Wilson of the University of Edinburgh says: "Our research highlights the fact that it's important to understand how stem cells work during embryo development. Knowing for the first time what key decisions cells make and when they make them means we can begin to work out how to influence the decision-making process. Once we can control the choices cells make, we're an important step closer to many medical applications."
The research was funded by the EU through its Framework 6 programme (EuroStemCell integrated project, JDRF/EuroStemCell Bridge funds, "Cells into Organs Network of Excellence, a Marie-Curie IE Fellowship to Elena Tzouanacou), the Institut Pasteur, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC).