Conditional telomerase induction causes proliferation of hair follicle stem cells
Conditional telomerase induction causes proliferation of hair follicle stem cells
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DOI：
10.1038/nature03836
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发表时间：
2005-08-18
期刊：
影响因子：
64.8
通讯作者：
Artandi, SE
中科院分区：
文献类型：
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作者：
Sarin, KY;Cheung, P;Artandi, SE
TERT 是端粒酶 (1,2) 的蛋白质成分，通过将端粒重复序列从头添加到染色体末端来维持端粒功能，并在 90% 的人类癌症中重新激活。在正常组织中，TERT 在干细胞和祖细胞中表达 (3)，但其在这些区室中的作用尚不完全清楚。在这里，我们表明，在小鼠皮肤上皮中条件性转基因诱导TERT，会导致从毛发生长终期（毛囊周期的静止期）快速转变为毛发生长初期（活跃期），从而促进毛发的强劲生长。 TERT 过度表达通过引起毛囊隆起区域的静止多能干细胞增殖来促进这种发育转变。 TERT 的这一新功能不需要端粒酶 RNA 成分（该成分编码端粒添加模板），因此通过与其合成端粒重复序列的活性无关的机制进行操作。这些数据表明，除了其在延长端粒方面的既定作用之外，TERT 还可以通过非规范途径促进静息干细胞的增殖。
TERT, the protein component of telomerase(1,2), serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells(3), but its role in these compartments is not fully understood. Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen ( the resting phase of the hair follicle cycle) to anagen ( the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component, which encodes the template for telomere addition, and therefore operates through a mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway.