Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Nat Commun. 2013;4:1946. doi: 10.1038/ncomms2946.
TRF1 is a component of the shelterin complex that protects chromosome ends. TRF1 deficiency leads to early embryonic lethality and to severe organ atrophy when deleted in adult tissues. Here we generate a reporter mouse carrying a knock-in eGFP-TRF1 fusion allele to study the role of TRF1 in stem cell biology and tissue homeostasis. We find that eGFP-TRF1 expression in mice is maximal in known adult stem cell compartments and show that TRF1 ensures their functionality. eGFP-TRF1 is highly expressed in induced pluripotent stem cells, uncoupled from the telomere elongation associated with reprogramming. Selection of eGFP-TRF1-high induced pluripotent stem cells correlates with higher pluripotency as indicated by their ability to form teratomas and chimeras. We further show that TRF1 is necessary for both induction and maintenance of pluripotency, and that TRF1 is a direct transcriptional target of Oct3/4.
TRF1 是保护染色体末端的庇护体复合物的一个组成部分。TRF1 缺乏会导致早期胚胎致死，当成年组织中缺失时会导致严重的器官萎缩。在这里，我们生成了一种携带 knock-in eGFP-TRF1 融合等位基因的报告小鼠，以研究 TRF1 在干细胞生物学和组织动态平衡中的作用。我们发现，eGFP-TRF1 在已知的成年干细胞隔室中的表达最高，并表明 TRF1 确保了它们的功能。eGFP-TRF1 在诱导多能干细胞中表达量很高，与与重编程相关的端粒延长脱偶联。eGFP-TRF1 高表达的诱导多能干细胞与更高的多能性相关，其形成畸胎瘤和嵌合体的能力表明了这一点。我们进一步表明，TRF1 对于诱导和维持多能性都是必需的，并且 TRF1 是 Oct3/4 的直接转录靶标。
