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. 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.

过氧化物酶体增殖物激活受体γ（Peroxisome Proliferator-Activated Receptor gamma, PPARG）是一类对胎盘发育至关重要的核受体转录因子。本研究以人滋养层干细胞（human trophoblast stem cells, TSCs）及其向绒毛外滋养层细胞（extravillous trophoblasts, EVTs）分化的模型为研究对象，证实PPARG同时参与TSC的自我更新与EVT分化过程。染色质免疫共沉淀测序（ChIP-seq）结果显示，PPARG在TSCs与EVTs中结合不同的调控元件集合，形成细胞类型特异性的转录调控网络。结合其他滋养层特异性转录因子的分析结果表明，PPARG在EVT分化过程中参与转录重编程。功能实验证实，PPARG的激活可促进EVT侵袭，提示PPARG信号通路与胎盘植入（placenta accreta）等胎盘病理状态存在潜在关联。本研究结果凸显了PPARG在人类滋养层发育过程中，通过调控基因表达与细胞行为发挥的情境特异性功能。本研究对不同培养条件下的人滋养层干细胞（TSCs）、分化第3天的绒毛外滋养层细胞（EVTd3）以及分化第8天的完全成熟绒毛外滋养层细胞（EVTd8）开展了RNA测序（RNA-seq）。