Abstract
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.
Highlights
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
Mouse ESCs are prototypical pluripotent cells, which are derived from the inner cell mass (ICM) of blastocysts[1,2] and possess similar gene expression patterns compared to ICM cells[3]
We show that Tcstv[1] and Tcstv[3] are involved in telomere length maintenance of mouse ESCs
Summary
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, Zscan[4], 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. 2C-gene Zscan[4] played important role in lengthening telomeres promptly by recombination-based mechanisms and maintaining genomic stability in ESCs7. It remains unclear whether other 2C-genes play a role in telomere length maintenance, self-renewal and pluripotency of ESCs. Tcstv[1] (2-cell-stage, variable group, member 1) and Tcstv[3] (2-cell-stage, variable group, member 3) are expressed predominantly in 2-cell embryos[18,19] and transiently in sporadic ESCs6,20. We show that Tcstv[1] and Tcstv[3] are involved in telomere length maintenance of mouse ESCs
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