TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis.
TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis.
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DOI：
10.1038/emboj.2011.199
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发表时间：
2011-06-21
期刊：
影响因子：
11.4
通讯作者：
Niemann, Catherin
中科院分区：
文献类型：
--
作者：
Petersson, Monika;Brylka, Heike;Kraus, Andreas;John, Susan;Rappl, Gunter;Schettina, Peter;Niemann, Catherin
哺乳动物表皮由毛囊间表皮、毛囊（HF）和相关的皮脂腺（SG）组成。它不断更新的干细胞和祖细胞群体已被确定，每个区室功能更新期间的细胞周转的不同机制。不同的干细胞（SC）池之间的功能关系是未知的，调节SC室的建立和维持的分子信号也没有很好地理解。在这里，我们进行了谱系追踪实验，以证明HF隆突SC的后代通过其他SC隔室转运，这表明一个层次的主管多能角质形成细胞有助于组织更新。凸起被鉴定为驱动HF的循环再生和SG的连续更新的双能SC隔室。我们的数据表明，TCF/Lef 1，对隆突SC活化和毛发分化至关重要的转录因子，异常信号传导导致源自隆突细胞的异位SG的发展。这种新生SG形成的过程伴随着新的祖先生态位的建立。详细的分子分析表明，组织形态发生的步骤重演。
Mammalian epidermis consists of the interfollicular epidermis, hair follicles (HFs) and associated sebaceous glands (SGs). It is constantly renewed by stem and progenitor cell populations that have been identified and each compartment features a distinct mechanism of cellular turnover during renewal. The functional relationship between the diverse stem cell (SC) pools is not known and molecular signals regulating the establishment and maintenance of SC compartments are not well understood. Here, we performed lineage tracing experiments to demonstrate that progeny of HF bulge SCs transit through other SC compartments, suggesting a hierarchy of competent multipotent keratinocytes contributing to tissue renewal. The bulge was identified as a bipotent SC compartment that drives both cyclic regeneration of HFs and continuous renewal of SGs. Our data demonstrate that aberrant signalling by TCF/Lef1, transcription factors crucial for bulge SC activation and hair differentiation, results in development of ectopic SGs originating from bulge cells. This process of de novo SG formation is accompanied by the establishment of new progenitor niches. Detailed molecular analysis suggests the recapitulation of steps of tissue morphogenesis.
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