EMBL scientists come a step closer to understanding skin, breast and other cancers
Stem cells have a unique ability: when they divide, they can either give rise to more stem cells, or to a variety of specialised cell types. In both mice and humans, a layer of cells at the base of the skin contains stem cells that can develop into the specialised cells in the layers above. Scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, in collaboration with colleagues at the Centro de Investigaciones Energ-ticas, Medioambientales y Tecnologicas (CIEMAT) in Madrid, have discovered two proteins that control when and how these stem cells switch to being skin cells. The findings, published online today in Nature Cell Biology, shed light on the basic mechanisms involved not only in formation of skin, but also on skin cancer and other epithelial cancers.
At some point in their lives, the stem cells at the base of the skin stop proliferating and start differentiating into the cells that form the skin itself. To do so, they must turn off the 'stem cell programme' in their genes and turn on the 'skin cell programme'. Researchers suspected that a family of proteins called C/EBPs might be involved in this process, as they were known to regulate it in other types of stem cell, but had so far failed to identify which C/EBP protein controlled the switch in skin. Claus Nerlov and his group at EMBL Monterotondo discovered it was not one protein, but two: C/EBPα and C/EBPβ.
The EMBL researchers used genetic engineering techniques to delete the genes that encode C/EBPα and β specifically in the skin of mouse embryos, and found that without these proteins the skin of the mice did not form properly.
"Mice with neither C/EBPα nor β had taut and shiny skin that couldn't keep the water inside their bodies", Nerlov explains, "they lacked many of the proteins that make skin mechanically strong and water tight, and they died of de-hydration shortly after birth".