Chiba et al. report that in human embryonic stem cells (hESCs, top), the promoter (green arrow) of the telomerase gene (TERT) is active, regardless of whether it is wild type (WT, left) or mutated (MUT, right). The telomerase enzyme (blue ellipse) maintains long telomeres at the chromosome ends. When the stem cells differentiate into fibroblasts or nerve cells (bottom), telomerase expression is appropriately down-regulated in cells with a wild type TERT promoter (grey arrow), and telomeres begin to shorten—which leads to senescence. However, this does not occur when cells with telomerase promoter mutations differentiate—which may allow the cells to become immortal.