Tissue regeneration - identification and characterization of new cell surface marker for skin stem cells

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Stat3 plays a crucial role in transducing a signal for migration of keratinocyte stem cells. To clarify the role of Stat3 in signaling the migration, we studied the intracellular signaling pathway through an integrin receptor in Stat3-deficient keratinocytes. Stat3-deficient keratinocytes demonstrated increased adhesiveness and fast spreading on a collagen matrix. Stat3-deficient keratinocytes had an increased number of tyrosyl-hyperphosphorylated focal adhesions. Analyses with immunoprecipitation revealed that p130Cas was constitutively hyperphosphorylated on tyrosine residues, while other focal adhesion molecules such as FAK and paxillin were not. These results strongly suggest that Stat3 in keratinocytes plays a critical role in turnover of tyrosine phosphorylation of p130Cas, modulating cell adhesiveness to the substratum leading to growth factor-dependent cell migration.The gene encoding a transmembrane glycoprotein LIG-1, of which extracellular region was organized with the leuci … More ne-rich repeats and immunoglobulin-like domains, was disrupted in mice by gene targeting. LIG-1-deficient mice developed a skin change on the tail and facial area after birth. The affected skin was histologically reminiscent of the epidermis in human common skin disease "psoriasis". The strong expression of LIG-1 mRNA in the bulge area of the hair follicles may suggest the strong expression of LIG-1 in the keratinocyte stem cells. Interestingly, the LIG-1 expression was apparently down-regulated in the psoriatic lesions, suggesting that LIG-1 is involved in the growth regulation of epidermal keratinocytes.Palms and soles differ from other body sites in terms of clinical and histologic appearance, response to mechanical stress, and the distribution of keratin 9. Because keratin 9 is exclusively expressed In the palmoplantar suprabasal keratinocyte layers, it is considered a differentiation marker of palms and soles. We studied palmoplantar mesenchymal influences on keratin 9 induction in nonpalmoplantar epidermis. Although nonpalmoplantar keratinocytes did not express keratin 9 mRNA when cultured with nonpalmoplantar fibroblasts, they did express it in cocultures with palmoplantar fibroblasts derived from papillary dermis. Pure epidermal sheets from nonpalmoplantar skin grafted on the human sole wounds showed transdifferentiation to palmoplantar phenotype and expressed keratin 9. Less