Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling

Trophoblast lineages, precursors of the placenta, are essential for post-implantation embryo survival. However, the regulatory network of trophoblast development remains incompletely understood. Here, we report that Cited1, a transcription coactivator, is a robust inducer for trophoblast-like state from mouse embryonic stem cells (ESCs). Depletion of Cited1 in ESCs compromises the trophoblast lineage specification induced by BMP signaling. In contrast, overexpression of Cited1 in ESCs induces a trophoblast-like state with elevated expression of trophoblast marker genes in vitro and generation of trophoblastic tumors in vivo. Furthermore, global transcriptome profile analysis indicates that ectopic Cited1 activates a trophoblast-like transcriptional program in ESCs. Mechanistically, Cited1 interacts with Bmpr2 and Smad4 to activate the Cited1–Bmpr2–Smad1/5/8 axis in the cytoplasm and Cited1–Smad4–p300 complexes in the nucleus, respectively. Collectively, our results show that Cited1 plays an important role in regulating trophoblast lineage specification through activating the BMP signaling pathway.