Abstract

The arising of trophectoderm (TE) is a hallmark event in preimplantation development during embryogenesis. However, little is known about the mechanisms underlying TE specification. Our findings demonstrate that depletion of Rif1 breaks down the barriers to conversion of trophoblast stem cells (TSCs). Rif1-null induced TSCs show typical TE properties, and differentiation potentials to terminal trophoblast lineages. Global transcriptome analysis reveals that Rif1-null activates 2-cell embryo (2C) related genes and induces a totipotent-like state, which is probably the main reason for the conversion of TSCs from Rif1-null embryonic stem cells (ESCs). Chimeric assays further confirm that Rif1-null ESCs can contribute to TE, further yielding TSCs in vitro . Over-expression of a downstream gene of Rif1, Hmgn3, can also activate 2C related genes and facilitate induction of TSCs. Here, we report two pioneer genes regulating conversion of TSCs and provide insights for investigating the mechanisms of TE specification.