Flores Ignacio, Canela Andres, Vera Elsa, Tejera Agueda, Cotsarelis George, Blasco María A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid E-28029, Spain.
Genes Dev. 2008 Mar 1;22(5):654-67. doi: 10.1101/gad.451008. Epub 2008 Feb 18.
Identification of adult stem cells and their location (niches) is of great relevance for regenerative medicine. However, stem cell niches are still poorly defined in most adult tissues. Here, we show that the longest telomeres are a general feature of adult stem cell compartments. Using confocal telomere quantitative fluorescence in situ hybridization (telomapping), we find gradients of telomere length within tissues, with the longest telomeres mapping to the known stem cell compartments. In mouse hair follicles, we show that cells with the longest telomeres map to the known stem cell compartments, colocalize with stem cell markers, and behave as stem cells upon treatment with mitogenic stimuli. Using K15-EGFP reporter mice, which mark hair follicle stem cells, we show that GFP-positive cells have the longest telomeres. The stem cell compartments in small intestine, testis, cornea, and brain of the mouse are also enriched in cells with the longest telomeres. This constitutes the description of a novel general property of adult stem cell compartments. Finally, we make the novel finding that telomeres shorten with age in different mouse stem cell compartments, which parallels a decline in stem cell functionality, suggesting that telomere loss may contribute to stem cell dysfunction with age.
鉴定成体干细胞及其所在位置（干细胞微环境）对再生医学具有重大意义。然而，在大多数成体组织中，干细胞微环境仍未得到很好的界定。在此，我们表明端粒最长是成体干细胞区室的一个普遍特征。利用共聚焦端粒定量荧光原位杂交技术（端粒图谱分析），我们发现组织内存在端粒长度梯度，端粒最长的区域对应已知的干细胞区室。在小鼠毛囊中，我们发现端粒最长的细胞对应已知的干细胞区室，与干细胞标志物共定位，并且在有丝分裂原刺激处理后表现出干细胞特性。利用标记毛囊干细胞的K15 - EGFP报告基因小鼠，我们发现绿色荧光蛋白阳性细胞具有最长的端粒。小鼠小肠、睾丸、角膜和大脑中的干细胞区室也富含端粒最长的细胞。这构成了对成体干细胞区室一种新的普遍特性的描述。最后，我们有了一个新发现，即在不同的小鼠干细胞区室中，端粒会随着年龄增长而缩短，这与干细胞功能的下降相平行，表明端粒丢失可能导致干细胞功能随年龄增长而出现障碍。
