Fig. 7

Schematic diagram showing distinct telomere regulation and retrotransposon transcription between naïve and primed cells. Telomeres lengthen significantly by telomerase and ALT pathway in naïve cells, which is associated with activation of the 2C genes and particularly sporadic expression of Zscan4. Repression of 2C genes including Dux in primed state cells is mainly caused by H3K9 methylation. While telomere elongation cannot be achieved by telomerase alone, telomere fragility occurs in primed cells, in association with decreased DNA recombination repair capacity. Naïve PSCs utilize both telomerase and telomere mechanisms to elongate telomeres, whereas primed PSCs have only telomerase to maintain telomeres. Nevertheless, the telomerase is insufficient after longer cultures of primed PSCs such that telomeres become shortened. Diverse inhibitory epigenetic modifications act together to regulate the retrotransposon transcription, resulting in specific expression of L1Md_T and IAPEz-int in naïve and primed cells, respectively. Moreover, decreased DNA repair capacity, aberrant transcription and insertion of retrotransposons are linked to increased genome instability in primed PSCs