Telomere reprogramming early in development and cloning

Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but low or absent in mature oocytes and cleavage stage embryos, and high again in blastocysts. How early embryos reset telomere length remains poorly understood. We show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. We further suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onward telomerase only maintains the telomere length established by this alternative mechanism. It is also interesting to note that telomeres are reprogrammed in cloned calves following nuclear transfer and that telomeres are lengthened in cloned mice with each generation. Yet, when and how telomere length is regulated in cloned embryos remains poorly understood. Interestingly, our work shows that telomere reprogramming might be length dependent. We also found that appropriate telomerase activity is required for differentiation of stem cells. Our findings that telomeres lengthen considerably during early cleavages may help clarifying the basic questions of how telomeres reset during development, and have implications for the study of stem cell and regenerative biology, aging and cancer biology.