We have further characterized Zscan4 in mouse 2-cell embryos and in the subpopulation of mouse ES cells. We found that other 2-cell-specific genes are also highly expressed in Zscan4(+) cells. This indicates that the subpopulation of ES cells marked by Zscan4 expression shows some resemblance to 2-cell embryos, whereas the majority of ES cells show similarity to the Inner Cell Mass (ICM) cells in blastocysts. Zscan4 is thus associated with a unique transient state in undifferentiated ES cells, in which other 2-cell embryo-specific genes are activated. By carrying out cell lineage tracing experiments, we have found that, although Zscan4 is expressed only in 5% of ES cells in culture at a given time, essentially all the ES cells experience Zscan4-positive state by 9 passages. By knocking down Zscan4 activation by an shRNA, we have found that Zscan4 is essential for long-term maintenance of genomic integrity and to mediate a regulated telomere recombination in normal undifferentiated ES cells, therefore making it indispensable for proper long-term self-renewal in ES cells. We have also found that Zscan4 is involved in the induction and recruitment of the meiosis-specific homologous recombination machinery to telomeres. We are currently investigating whether the activation of Zscan4 can further increase the genome stability in ES and induced pluripotent (iPS) stem cells.
| Zalzman, Michal; Falco, Geppino; Sharova, Lioudmila V et al. (2010) Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature 464:858-63 |
| Nishiyama, Akira; Xin, Li; Sharov, Alexei A et al. (2009) Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell 5:420-33 |
| Stanghellini, Ilaria; Falco, Geppino; Lee, Sung-Lim et al. (2009) Trim43a, Trim43b, and Trim43c: Novel mouse genes expressed specifically in mouse preimplantation embryos. Gene Expr Patterns 9:595-602 |
