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- W4315706463 abstract "Hypertensive disorders in pregnancy, of which the multisystem syndrome pre-eclampsia is most severe, leading to preterm delivery, maternal mortality and life-long complications1. Pre-eclampsia lacks early screening tools2,3 and causal therapies4,5. To elucidate early disease dynamics, we present the first spatio-temporal study comparing single-nuclei transcriptomes of human preterm pre-eclamptic placentae and healthy controls, contextualising this in a comprehensive study including early and late gestational placentae and implementing spatial multi-omics methods. Here we show trophoblast pre-fusion cells and their developmental trajectory running towards a novel trophoblast cell-state we identify as juvenile syncytiotrophoblast. We found that disturbed trophoblast development, reconstructed by spatial multi-omics and including early dysregulation in differentiation-driving transcription factor p300, likely initiates pre-eclampsia. We suggest pre-eclampsia to be a disease of dysregulated syncytiotrophoblast differentiation: Disease-specific premature differentiation of the maternal-foetal barrier leads to a senescent syncytiotrophoblastic interaction through maternal circulation with maternal vessels. This initiates a disrupted decidual maternal response via LEP, GDF15 and INHBA. Our results highlight a disturbed cellular communication from foetal to maternal side during the development of pre-eclampsia starting with a disturbed trophoblast maturation. We provide new targets for potential early disease prevention in order to protect mother and child from increased gestational mortality and morbidity but also from life-long increased cardiovascular disease risk." @default.
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- W4315706463 date "2023-01-01" @default.
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- W4315706463 title "PS-B05-11: IMPAIRED CELL INTERACTIONS AT THE PRE-ECLAMPTIC MATERNAL-FOETAL INTERFACE" @default.
- W4315706463 doi "https://doi.org/10.1097/01.hjh.0000916520.83656.b0" @default.
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