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000297968 245__ $$aThe spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms.
000297968 260__ $$aCambridge, Mass.$$bCell Press$$c2025
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000297968 520__ $$aThe labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms. Spatiotemporal transcriptomic profiling identified a gradual change in the expression of epigenetic enzymes, including the de novo DNA methyltransferase 3a (DNMT3A). Loss of Dnmt3a resulted in DNA hypomethylation and perturbation of zonated placental gene expression. The resulting global DNA hypomethylation impaired the angiogenic capacity of endothelial cells. Global or endothelium-predominant deletion of Dnmt3a resulted in impaired placental vascularization and fetal growth retardation (FGR). Human placental endothelial gene expression profiling associated preeclampsia with reduced DNMT3A expression. Collectively, our study identified DMNT3A as critical methylome-regulator of placental endothelial gene expression and function with clinical implications for placental dysfunction, as it occurs during preeclampsia or FGR.
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000297968 650_7 $$2Other$$aDNA methylation
000297968 650_7 $$2Other$$aDNMT3A
000297968 650_7 $$2Other$$aangiogenesis
000297968 650_7 $$2Other$$aepigenetic regulation
000297968 650_7 $$2Other$$agrowth retardation
000297968 650_7 $$2Other$$aplacental endothelium
000297968 650_7 $$2Other$$aspatial zonation
000297968 7001_ $$0P:(DE-He78)e17ab05b2c7ece91a9ce3e8355fd3825$$aJakab, Moritz Viktor$$b1
000297968 7001_ $$aGutjahr, Ewgenija$$b2
000297968 7001_ $$aGu, Zuguang$$b3
000297968 7001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b4$$udkfz
000297968 7001_ $$0P:(DE-He78)697cb039ca08f3b7e5a2a52dbf020b46$$aMallm, Jan-Philipp$$b5$$udkfz
000297968 7001_ $$aMogler, Carolin$$b6
000297968 7001_ $$aSchlesner, Matthias$$b7
000297968 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b8$$udkfz
000297968 7001_ $$0P:(DE-He78)e674edaa6403c4ef34b2fae4649e654f$$aSchlereth, Katharina$$b9$$eLast author
000297968 7001_ $$0P:(DE-He78)2e92d0ae281932fc7347d819fec36b0b$$aAugustin, Hellmut$$b10$$eLast author$$udkfz
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