How stem cells make skinSeptember 14, 2009EMBL 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 Energéticas, 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". However, a single working copy of either the gene for C/EBPα or the gene for C/EBPβ was enough to ensure that skin developed properly. This means that the two proteins normally do the same job in the skin's stem cells - an unexpected redundancy, which may have arisen because there are so many stem cells in skin that a tight control on proliferation is needed to avoid problems like cancer. Or it may simply be a by-product of the fact that these two proteins have different functions in other situations, such as wound healing or repair of sunlight-induced skin damage. One of the hallmarks of epithelial cancers - which include skin, breast, and oral cancers - is that they have genes turned on which would normally only be expressed in embryonic stem cells, and which may help cancer cells divide indefinitely. Such genes become re-expressed in the skin in the absence of C/EBPs. So, by understanding how C/EBPα and β turn off such 'stem cell' programmes, researchers hope to come a step closer to finding ways to fight such cancers. When Nerlov and colleagues looked at how C/EBPα and -β work in the skin, they found that these proteins also regulate a number of other molecules that control skin development. Several important pathways known to control skin and hair formation were improperly activated in the mice lacking C/EBPα and -β. "This is a very important discovery", says Nerlov. "It opens up a lot of new areas, because we can see how these proteins control virtually every other molecule known to regulate skin cell differentiation. It seems to be a key piece in the puzzle of how our skin is formed and maintained throughout life." European Molecular Biology Laboratory |
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| Related Stem Cells Current Events and Stem Cells News Articles New discovery about the formation of new brain cells The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells. Umbilical cord blood stem cell transplant may help lung, heart disorders Two separate studies published in the current issue of Cell Transplantation (18:8), - now freely available on-line have shown that transplanted human-derived umbilical cord blood (UCB) stem cells transplanted in an animal model had positive therapeutic effects on specific lung and heart disorders the animal models. Gene mismatch influences success of bone marrow transplants A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics. New research shows versatility of amniotic fluid stem cells For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought. First reconstitution of an epidermis from human embryonic stem cells Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells. Bone Implant Offers Hope for Skull Deformities A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon. Your Own Stem Cells Can Treat Heart Disease The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells. Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines? Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure. Paradoxical protein might prevent cancer One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell. U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning. More Stem Cells Current Events and Stem Cells News Articles |
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