Abstract：
The basal layer of human interfollicular epidermis has been described to harbour both quiescent keratinocyte stem cells and a transit amplifying cell population that maintains the suprabasal epidermal layers. We performed immunofluorescence analyses and revealed that the main proliferative keratinocyte pool in vivo resides suprabasally. We isolated from the human epidermis two distinct cell populations, the basal and the suprabasal keratinocytes, according to the expression of integrin β4 (iβ4). We compared basal iβ4+ or suprabasal iβ4- keratinocytes with respect to their proliferation and colony-forming ability and their Raman spectral properties. In addition, we generated dermo-epidermal substitutes using freshly isolated and sorted basal iβ4+ or suprabasal iβ4- keratinocytes and transplanted them on immuno-compromised rats. We show that suprabasal iβ4- keratinocytes acquire a similar proliferative capacity as basal iβ4+ keratinocytes after two weeks of culture in vitro, with expression of high levels of iβ4 and downregulation of K10 expression. In addition, both basal iβ4+ and suprabasal iβ4- keratinocytes acquire authentic self-renewing properties during the in vitro 3D-culture phase and are able to generate and maintain a fully stratified epidermis for 16 weeks in vivo. Therefore, against the leading dogma, we propose that human suprabasal keratinocytes can retro-differentiate into true basal stem cells in a wound situation and/or when in contact with the basement membrane.
摘要：
已经描述了人毛囊间表皮的基底层既包含静止的角质形成细胞干细胞，又包含维持鼻上表皮层的转运扩增细胞群。我们进行了免疫荧光分析，发现体内主要的增殖角质形成细胞池位于鼻上。我们从人类表皮中分离出两种不同的细胞群，基底和基底上角质形成细胞，根据整合素β4(iβ4)的表达。我们比较了基底iβ4或基底iβ4-角质形成细胞的增殖和集落形成能力以及拉曼光谱特性。此外,我们使用新鲜分离和分选的基底iβ4或基底上iβ4-角质形成细胞产生了真皮表皮替代品，并将其移植到免疫受损的大鼠上。我们显示，体外培养两周后，基底iβ4-角质形成细胞获得与基底iβ4+角质形成细胞相似的增殖能力，与高水平的iβ4表达和K10表达下调。此外,基底iβ4+和基底iβ4-角质形成细胞在体外3D培养阶段均获得真正的自我更新特性,并且能够在体内生成并维持16周的完全分层表皮.因此,反对主要的教条，我们认为，在创伤情况下和/或与基底膜接触时，人类基底上角质形成细胞可以向后分化为真正的基底干细胞。
