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Epidermal stem cell clusters

Stem cells in the basal layer of human interfollicular epidermis form clusters that can be reconstituted in vitro. In order to supply the interfollicular epidermis with differentiated cells, the size of these clusters must be controlled. Evidence suggests that control is regulated via differentiation of stem cells on the periphery of the clusters. Moreover, there is growing evidence that this regulation is mediated by the Notch signalling pathway. In this work, we developed theoretical arguments, in conjunction with computer simulations of a model of the basal layer, to show that regulation of differentiation is the most likely mechanism for cluster control. In addition, we showed that stem cells must adhere more strongly to each other than they do to differentiated cells. We also showed that lateral-induction, mediated by the Notch signalling pathway, is a natural mechanism for cluster control. It can not only indicate to cells the size of the cluster they are in and their position within it, but it can also control the cluster size. This can only be achieved by postulating a secondary, cluster wide, differentiation signal, and cells with high Delta expression being deaf to this signal.

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This work was published in Developmental Biology.


Psoriasis is a common skin disease seen as red scaly patches on the skin, especially the joints and the scalp. The disease is heritable but not contagious. It can first appear at any time in a persons life and can be brought about by any number of factors including adolescence or stress. The disease can be treated with creams applied to the skin but it is not curable; the lesions may reappear continuously throughout a perons life.

Skin is composed of two layers. The outermost layer is made up of skin cells including the dead surface cells that slough off. The innermost layer is made up of fibres and blood vessels. The fibers anchor the skin's cells to the body and give skin its elasticity. In normal skin the outermost layer is about 0.1mm thick. In psoriatic skin this layer is much thicker with a large buildup of dead cells that flake off as scales. The blood vessels become wider increasing blood flow to the skin and giving the lesions their red appearence.

The skin is thought to become thicker because some cells grow and divide more rapidly than normal. This is what we tried to model with computer simulations.

This movie shows the nitrix oxide (left) and peroxynitrite (right) concentrations in a simulated 2D section of a developing psoriatic plaque with three capillaries. Black represents low concentrations and yellow high concentrations. This movie shows the collagen density in the same plaque. Black represents the epidermis, blue the basal cells, dark red the capillaries and red-yellow increasing collagen density.

This work was published in the Journal of Theoretical Biology.

Document made with Nvu Created 11 April 2007.