Mechanisms of transcription factor-mediated direct reprogramming of mouse embryonic stem cells to trophoblast stem-like cells

Direct reprogramming can be achieved by forced expression of transcription factors (TFs). Yet how such TFs mediate repression of initial cell-type-specific genes while activating target cell-type-specific genes is unclear. Here, we achieve embryonic stem (ES) to trophoblast stem (TS)-like cell reprogramming by introducing individual TS-specific “CAG” factors (Cdx2, Arid3a, Gata3). We interrogated their chromosomal target occupancies, modulation of global transcriptome and chromatin accessibility at the initial stage of reprograming. Our findings uncovered a sequential, two-step mechanism of cellular reprogramming in which repression of exiting ES pluripotency is followed by activated conversion to TS cells by CAG factors. Overall design: TS-like cells were generated from ES cells using CAG factors, followed by deep sequencing, using Illumina