BAP1 dysregulation impairs trophoblast differentiation and contributes to placental dysfunction in preeclampsia
Doria Borrell, P.; Ferrero Mico, A.; Navarro Serna, S.; Mellado Lopez, M.; Grinat, J.; Murphy, C. N.; Youssef, L.; Crispi, F.; Kaitu'u Lino, T. J.; Perez Garcia, V.
Show abstract
Preeclampsia, a life-threatening hypertensive disorder of pregnancy, is a leading cause of maternal and perinatal morbidity and mortality. Its early-onset form (EO-PE), requiring delivery before 34 weeks of gestation, is particularly severe and closely linked to defective trophoblast differentiation. Here, we identify BRCA1-associated protein 1 (BAP1) and its cofactors ASXL2 and ASXL3 are upregulated in EO-PE placentas. Enforced BAP1 expression in human trophoblast stem cells reinforced epithelial identity, enhanced adhesion, and impaired both extravillous trophoblast differentiation and syncytiotrophoblast formation. Integrated transcriptomic and proteomic analyses revealed suppression of lineage-specific pathways alongside maintenance of progenitor-like and pro-inflammatory signatures. In trophoblast organoids, excess of BAP1 disrupted syncytial maturation and induced interferon-driven pathways overlapping with EO-PE transcriptomes. Together, these findings establish BAP1 as a key regulator of human trophoblast differentiation and implicate its dysregulation in the pathogenesis of EO-PE, providing mechanistic insight into the cellular basis of placental dysfunction.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single Cell Transcriptional Signatures of the Human Placenta in Term and Preterm Parturition 97%
- Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing 96%
- Regionally distinct trophoblast regulate barrier function and invasion in the human placenta 96%
Similar papers in this journal
- TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development 95%
- Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth 95%
- Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids 93%
Similar papers in this journal
- Decoding human placental cellular and molecular responses to maternal obesity and fetal growth 95%
- M2 Macrophages are Major Mediators of Germline Risk of Endometriosis and Explain Pleiotropy with Comorbid Traits 93%
- Circulating tumor cells shed shearosome extracellular vesicles in capillary bifurcations that activate endothelial and immune cells 93%
Similar papers in this journal
- Maternal obesity and offspring neurodevelopment are associated with hypoxic gene expression in term human placenta 95%
- Detailed Survey of an in-vitro Intestinal Epithelium Model by Single-Cell Transcriptomics 93%
- Comparing the impact of sample multiplexing approaches for single-cell RNA-sequencing on downstream analysis using cerebellar organoids 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.