Journal Article

DKFZ-2025-00145

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms.

Gehrs, S. (First author)DKFZ* ; Jakab, M. V.DKFZ* ; Gutjahr, E. ; Gu, Z. ; Weichenhan, D.DKFZ* ; Mallm, J.-P.DKFZ* ; Mogler, C. ; Schlesner, M. ; Plass, C.DKFZ* ; Schlereth, K. (Last author)DKFZ* ; Augustin, H. (Last author)DKFZ*

2025
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.devcel.2024.12.037

Abstract: The 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.

Keyword(s): DNA methylation ; DNMT3A ; angiogenesis ; epigenetic regulation ; growth retardation ; placental endothelium ; spatial zonation

Note: #EA:A190#LA:A190# / 2025 May 19;60(10):1467-1482.e8

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Contributing Institute(s):

1. A190 Vaskuläre Onkologie und Metastasierung (A190)
2. Epigenomik (B370)
3. B066 Chromatin-Netzwerke (B066)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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