Fig. 5: BAP1 overexpression disrupts trophoblast organoid formation and recapitulates early-onset preeclampsia features. | Cell Death & Disease

Fig. 5: BAP1 overexpression disrupts trophoblast organoid formation and recapitulates early-onset preeclampsia features.

From: BAP1 dysregulation impairs trophoblast differentiation and contributes to placental dysfunction in preeclampsia

Fig. 5: BAP1 overexpression disrupts trophoblast organoid formation and recapitulates early-onset preeclampsia features.The alternative text for this image may have been generated using AI.

A Brightfield images of BAP1-OE and control organoids, demonstrating comparable morphology and size. Scale bar, 150 µm. B Immunofluorescence (IF) staining of BAP1-OE and control organoids for CDH1 and SDC1. Nuclear counterstaining was with DAPI. Scale bars, 150 µm. C RT-qPCR analysis of STB (SDC1, CGB, ERVW-1, and ERVFRD-1), BAP1, stem cell (TFAP2C) and villous cytotrophoblast cell column (ITGA2, ITGB6) markers in BAP1-OE and control organoids (mean ± SEM, n = 4 independent experiments; **p < 0.005, ***p < 0.001, ****p < 0.0001; Student two-tailed t-test). D Western blot analysis of BAP1, GFP-BAP1, and SDC1 in BAP1-OE and control organoids, with ACTIN or HSP90 used as loading controls, as indicated. Each target protein was normalized to its corresponding loading control within the same experiment. Quantification of relative BAP1 and SDC1 protein levels, expressed relative to control organoids, is shown at the bottom (mean ± SEM, n = 3 independent experiments; p < 0.05, **p < 0.001; Student’s two-tailed t-test). E GO enrichment analysis of differentially expressed genes (DEGs) in BAP1-OE vs control organoids. F Heatmap showing representative proteins from the BAP1-OE signature that are also dysregulated in PE, with downregulation of DUSP9, ADAMTS1, and COL1A2, and upregulation of AFAP1 and FLT1 in BAP1-OE organoids. Colour scale indicates scaled expression values (red, upregulation; blue, downregulation). G (Upper panel) Principal component analysis (PCA) plots showing the distribution of early-onset preeclampsia (EO-PE) samples (red) and controls (green) from the GSE190171 EO-PE-affected dataset, based on the BAP1-OE molecular signature. The X and Y axes represent principal components 1 and 2, which explain the indicated percentage of total variance. (Lower panel) Unsupervised hierarchical clustering of EO-PE (red) and control (green) samples from each dataset, based on the BAP1 gene signature. OE, overexpression; STB, syncytiotrophoblast.

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