Scientists have discovered that an epigenetic mark guides the development of stem cells.
Photo courtesy of © (2007) istockphoto.com/Dan Brandenburg
Epidermal stem cells are restricted to producing only ten differentiated layers; in contrast, embryonic stem cells have the ability to develop into any type of human cell. So what exactly causes epidermal stem cells to restrict their fate? This is the question a team of scientists at the Rockefeller University set out to investigate, releasing their findings in the March 20 issue of Cell. They discovered that an epigenetic mark guides the development of epidermal stem cells in mouse embryos. Such findings have great significance in the evolution of sophisticated therapeutic skin treatments.
Fuchs and Ezhkova, both from the Laboratory of Mammalian Cell Biology and Development, found that the polycomb repressor complex (a complex of proteins) that hampers access to genes decreased in expression as the differentiation of epidermal cells commenced. Concurrently, the transcription factor AP1 that activates genes increased in expression. Of particular note is the gene Ezh2 found in the polycomb repressor complex, which effectively ‘blocks’ the cell from reading small sections of DNA by attaching a molecular clamp to the appropriate gene. The transcription factors cannot move past this physical barrier, thereby controlling the growth of epidermal skin cells.
The team from Rockefeller University bred mice with and without Ezh2. The results showed that mice without Ezh2 had thicker skin than the control group, as Ezh2 was not present to refuse access to the skin differentiation genes. This allowed skin to build up layer after layer. Intriguingly, they found that only the skin differentiation genes of the epidermal stem cells were activated. This can be attributed to AP1, which is found in both stem and differentiating cells. Without the presence of Ezh2, AP1 is free to activate the stem cell genes earlier than desired, leading to increased growth of skin. Furthermore, non-skin genes in epidermal stem cells lack the epigenetic markers required to switch those genes on. Ultimately, the non-skin genes are kept silent, allowing only the ’right’ programming (that is, the skin cells) to function.
The Rockefeller researchers envisage that this discovery will become highly valuable for skin generation technology, particularly in the case of prematurely-born babies without fully-formed skin. This is a fascinating insight into the incredibly complex world of genes. We cannot deny that our understanding of genetics is somewhat crude; thus, with research such as this we must continue to aspire to fill in the missing parts of the jigsaw for the betterment of our society.
By Sarah Walton, 42065950
Resources
Ezhkova, E., H. A. Pasolli, et al. (2009). "Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells." Cell 136(6): 1122-1135.
Rockerfeller University (2009, March 19). Epigenetic mark Guides Stem Cells Toward Their Destiny. ScienceDaily. Retrieved March 23, 2009, from http://www.sciencedaily.com/releases/2009/03/090319132921.htm
