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

STAT3在角质形成干细胞迁移信号的传导中起着至关重要的作用。为了阐明STAT3在迁移信号中的作用，我们研究了STAT3缺陷角质形成细胞中通过整合素受体的细胞内信号通路。STAT3缺失的角质形成细胞表现出更高的粘附性和在胶原基质上的快速铺展。STAT3缺陷的角质形成细胞有更多的酪氨酰过度磷酸化的局灶性粘连。免疫沉淀分析表明，p130Cas在酪氨酸残基上被结构性过度磷酸化，而其他焦点黏附分子如FAK和paxlin不是。这些结果有力地表明，角质形成细胞中的STAT3在p130Cas酪氨酸磷酸化的翻转过程中起着关键作用，调节细胞与底物的粘附性，导致生长因子依赖的细胞迁移。编码跨膜糖蛋白LIG-1的基因是由Leuci…组成的更多富含Ne的重复序列和免疫球蛋白样结构域，在小鼠中被基因靶向破坏。Lig-1基因缺陷的小鼠出生后尾巴和面部出现皮肤变化。受影响的皮肤组织学上类似于人类常见皮肤病“牛皮癣”中的表皮。毛囊隆起区LIG-1mRNA的强表达可能提示角质形成干细胞中有LIG-1的强表达。有趣的是，LIG-1在银屑病皮损中的表达明显下调，提示LIG-1参与了表皮角质形成细胞的生长调节。手掌和脚底在临床和组织学形态、对机械应力的反应以及角蛋白9的分布方面与其他身体部位不同。由于角蛋白9仅在掌底上基底层角质形成细胞层中表达，因此被认为是手掌和脚掌的分化标志。我们研究了掌趾间充质对非掌跖表皮角蛋白9诱导的影响。虽然非掌足部角质形成细胞在与非掌足部成纤维细胞共培养时不表达角蛋白9，但在与真皮乳头状部的掌足部成纤维细胞共培养时，角蛋白9确实表达。人足底创面上移植的非掌底皮肤的纯表皮片可转分化为掌跖表型，并表达角蛋白9。

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