Human telomeres play critical roles in protecting chromosome ends and preserving genomic integrity. Telomerase, essential for maintaining telomere length and cellular replicative capacity, is only expressed in a small subset of human cells: stem and progenitor populations. Conversely, most somatic cells’ telomeres shorten with each cell division; this shortening provides a potent tumor suppressor mechanism. Thus, telomerase regulation shapes not only cellular life span and differentiation, but also the regenerative capacity and long-term integrity of tissues. Here, we review the current understanding of telomere length control and telomerase regulation in humans, from molecular interactions at chromosome ends to the tissue-specific variation of telomere length dynamics, drawing insight from pluripotent and adult stem cell populations, as well as telomerase dysregulation in cancer and telomere biology disorders.
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