The authors used RNA sequencing to identify a transient population of cells that resemble two cell embryos within induced pluripotent stem cell and embryonic stem cell populations. This population is totipotent, which means that it is able to produce cells from both embryonic and extraembryonic tissues, and its transient formation is regulated by histone modifications. Furthermore, many of the activated two-cell-stage transcripts in this transient population have regulatory elements derived from endogenous retroviruses, suggesting that these foreign sequences can be key regulators of cell fate.