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Abstract: Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated glutaminyl-peptide cyclotransferase-knockout (Qpct^-/-) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identifiedQpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared withQpct^+/+ mice, placentae and embryos (Qpct^-/+ andQpct^-/-) showed significant overgrowth at embryonic Day 12.5 (E12.5), E15.5, and E18.5. Using single-cell transcriptome analysis of 32 309 cells fromQpct^+/+ andQpct^-/- mouse placentae, we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880Qpct^+/+ and 13 577 Qpct^-/- cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567Qpct^+/+ and 3285Qpct^-/- cells). Furthermore, we observed a global up-regulation of pro-angiogenic genes in theQpct^-/- background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5Qpct^-/+ andQpct^-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternalQpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.

单细胞转录组分析揭示印迹基因谷氨酰基环化酶缺失导致异常的血管生成和胎盘形成

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