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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE295569 | GEO | 2025/06/24

REPOSITORIES: GEO

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

Project description: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.

2025-06-24 | GSE278375 | GEO

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

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

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scRNA-seq and snucRNA-seq of human primary trophoblast organoids (PTO) and trophoblast stem cells (TSCs) differentiation into extravillous trophoblast organoids (EVTs)

Project description:This study aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. The study includes two type of systems: human primary trophoblast organoids (PTO) and trophoblast stem cells (TSCs). Trophoblast stem cell (TSC) lines BTS5 and BTS11 derived by Okae and colleagues were grown as described previously (Okae et al. 2018) and together with EVT media. Primary trophoblast organoids (PTO) were grown and differentiated into EVT as previously described by Turco & Sheridan (Turco et al 2018; Sheridan et al 2020). This study shows that the main regulatory programs mediating EVT invasion in vivo are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells.

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Project description:Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be directed to differentiate into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) protein, mRNA, and miRNA cargo, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.

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