PPARG-centric transcriptional re-wiring during differentiation of human trophoblast stem cells into extravillous trophoblasts [RNA-seq]

Peroxisome Proliferator-Activated Receptor gamma (PPARG) is a nuclear receptor transcription factor critical for placental development. Using human trophoblast stem cells (TSCs) and their differentiation into extravillous trophoblasts (EVTs) as a model, we show that PPARG is required for both TSC self-renewal and EVT differentiation. ChIP-seq revealed that PPARG occupies distinct sets of regulatory elements in TSCs and EVTs, forming cell-type specific transcriptional networks. Integration with other trophoblast-specific transcription factors suggests that PPARG participates in transcriptional re-wiring during EVT differentiation. Functionally, activation of PPARG promotes EVT invasion, suggesting a potential connection between PPARG signaling and placental pathologies such as placenta accreta. These findings highlight context-specific roles of PPARG in modulating gene expression and cell behavior during human trophoblast development. Overall design: RNA-seq was conducted on human trophoblast stem cells (TSCs), extravillous trophoblasts (EVTs) at differentiation day 3 (EVTd3), and fully differentiated EVTs at day 8 (EVTd8) under various conditions.