Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany.
Curr Med Chem. 2012;19(35):5984-92.
The skin epithelium undergoes constant renewal, a process that is driven by stem cells (SCs) localising to the interfollicular epidermis and different regions of the hair follicle. Over the last years, tremendous progress has been made to unravel the physiological function of distinct stem and progenitor cell populations by using genetic lineage tracing in vivo, transplantation, clonogenicity approaches and live cell imaging. It turned out that these cell compartments constitute heterogeneous SC pools and that individual SCs respond differently to various signals sent by the microenvironment. Recent genetic manipulation experiments and elegant mouse models have shed light on the signalling pathways being crucial for self-renewal and lineage fate decisions during tissue homeostasis. Here, we summarise current concepts of SC function in mammalian skin and focus on the dynamic behaviour of SCs during morphogenesis and tissue regeneration of the skin epithelium. Clearly, understanding the cellular and molecular mechanisms of SC regulation and function during tissue homeostasis has enormous impact on our view of the pathogenesis of various skin diseases and will be beneficial for regenerative medicine. Recent experiments suggest an important role of tissue SCs in the process of skin tumour initiation and progression. For the future, the genuine challenge is to further dissect SC function in pathophysiological settings and to translate our knowledge to design novel efficient therapeutic strategies for treatment of cutaneous cancer.
皮肤上皮经历持续的更新，这个过程由定位于毛囊间表皮和不同区域的干细胞（SCs）驱动。在过去的几年中，通过体内遗传谱系追踪、移植、克隆形成和活细胞成像等方法，人们在揭示不同干细胞和祖细胞群体的生理功能方面取得了巨大进展。事实证明，这些细胞区室构成了异质的 SC 池，并且单个 SC 对微环境发出的各种信号的反应不同。最近的遗传操作实验和巧妙的小鼠模型揭示了信号通路在组织稳态过程中的自我更新和谱系命运决定中至关重要。在这里，我们总结了哺乳动物皮肤中 SC 功能的当前概念，并重点介绍了 SC 在皮肤上皮形态发生和组织再生过程中的动态行为。显然，了解组织稳态过程中 SC 调节和功能的细胞和分子机制，对我们了解各种皮肤疾病的发病机制具有巨大影响，并将有益于再生医学。最近的实验表明，组织 SC 在皮肤肿瘤起始和进展过程中具有重要作用。未来的真正挑战是进一步剖析生理病理条件下的 SC 功能，并将我们的知识转化为设计治疗皮肤癌的新型有效治疗策略。
