Effect of the topography of the human epidermal-dermal junction in influencing stem cell behaviour

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The epidermis is the outer covering of the skin and plays an essential role in protecting our bodies from bacteria and other pathogens. It is made up of multiple layers of cells that are stacked on top of one another. The deepest cell layer, furthest from the skin surface, contains stem cells. Their role is to divide throughout our lives to make more cells that subsequently mature as they move through the upper cell layers. The most mature cells are specialised to form a protective barrier on the skin surface. If a tiny piece of skin is removed from the body and taken to the laboratory, it is possible to grow sheets of epidermis that have similar properties to normal epidermis and indeed these sheets can be used to repair burns and other types of skin wound. One interesting feature of human epidermis is that the stem cells are clustered in specific positions in the basal cell layer, which correlate with natural undulations in the boundary between the epidermis and the underlying connective tissue. As we age the undulations become much less pronounced, but in contrast in some common skin diseases such as psoriasis the undulations become more prominent. We would like to understand why the stem cells are clustered in this way and whether the size of the undulations affects their behaviour. To investigate this we will grow human epidermal cells on special surfaces made out of artificial materials, such as the rubbery substance used as bath sealant, that recreate the undulations. We will measure whether cells in different positions on these surfaces are more likely to remain as stem cells or to leave the basal layer and mature. We will investigate whether on substrates that resemble aged skin the cells show an altered ability to divide and mature. We will discover how the substrates direct the stem cells to behave by identifying the signalling events that take place inside the stem cells. We will also find out whether we can over-ride the effects of the substrates by artificially stimulating changes in gene expression inside the cells.The outcome of the project will be to explain, for the first time, why stem cells lie in specific locations in human epidermis and whether the information provided by their location contributes to the changes in the epidermis that are linked to skin ageing.