MSX2 safeguards syncytiotrophoblast fate of human TSCs

The majority of placental pathologies arise from failures in trophoblast differentiation, yet the underlying transcriptional regulation is poorly understood. Here, we use human trophoblast stem cells to elucidate the function of the transcription factor MSX2 in trophoblast specification. We show that depletion of MSX2 de-represses the syncytiotrophoblast program, while forced expression of MSX2 blocks it. We demonstrate that a large proportion of the affected genes are directly bound and regulated by MSX2 and identify components of the SWI/SNF complex as its strong interactors. Our findings uncover the pivotal role of MSX2 in cell fate decisions that govern human placental development and function. RNAseq of MSX2 KD and control hTSCs in self-renewing conditions and MSX2 inducible overexpression in syncytiotrophoblast differentiated from hTSCs. ChIPseq data of MSX2 in hTSC.