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Mouse embryonic stem cell (ESC) cultures exhibit a heterogeneous mixture of metastable cells sporadically entering the 2-cell (2C)-embryo-like state, critical for ESC potency. One of 2-cell genes,  Zscan4,  has been shown to be responsible for telomere maintenance, genomic stability and pluripotency of mouse ESCs. Functions of other 2C-genes in ESCs remain elusive. Here we show that 2C-genes  Tcstv1  and  Tcstv3  play a role in regulation of telomere lengths. Overexpression or knockdown  Tcstv1  and  Tcstv3  does not immediately affect proliferation, pluripotency and differentiation  in vitro  of ESCs. However, ectopic expression of  Tcstv1  or  Tcstv3  results in telomere elongation, whereas  Tcstv1/3  knockdown shortens telomeres of ESCs. Overexpression of  Tcstv1  or  Tcstv3  does not alter telomere stability. Furthermore,  Tcstv1  can increase Zscan4 protein levels and telomere recombination by telomere sister chromatid exchange (T-SCE). Depletion of  Tcstv1/3  reduces Zscan4 protein levels. Together,  Tcstv1  and  Tcstv3  are involved in telomere maintenance that is required for long-term self-renewal of mouse ESCs. Our data also suggests that Tcstv1/3 may co-operate and stabilize Zscan4 protein but the molecular bases remain to be determined.

Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells