Stem cells within the human interfollicular epidermis occur in clusters but the molecular basis for this distribution is poorly understood. Legg et al. propose that melanoma chondroitin sulphate proteoglycan (MCSP), a new stem-cell marker, contributes to the spatial organisation of epidermal stem cells by regulating their adhesive properties (see p. 6049). The researchers show that expression of MCSP, a cell-surface proteoglycan, is restricted to those cells in the interfollicular epidermis that express the highest amounts ofβ1 integrin. These cells are non-cycling in vivo but form self-renewing clones in vitro, characteristics of epidermal stem cells. Interference with endogenous MCSP function by expression of a CD8/MCSP chimera, consisting of the extracellular domain of CD8 and the cytoplasmic domain of MCSP, did not affect the proliferation or differentiation of keratinocytes, but reduced their cohesiveness. Legg et al. conclude that MCSP is functionally important in promoting epidermal stem-cell clustering.

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