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USP7 缺失导致小鼠早期胚胎发育失败。

USP7 reduction leads to developmental failure of mouse early embryos.

机构信息

Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Basic Medicine, School of Medicine, Jinan University, Guangzhou, China; Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Guangdong Second Provincial General Hospital, Medical College, Jinan University, Guangzhou, China.

Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Guangdong Second Provincial General Hospital, Medical College, Jinan University, Guangzhou, China.

出版信息

Exp Cell Res. 2023 Jun 15;427(2):113605. doi: 10.1016/j.yexcr.2023.113605. Epub 2023 Apr 18.

DOI:10.1016/j.yexcr.2023.113605
PMID:37080417
Abstract

As a member of Ubiquitin-specific protease subfamily, ubiquitin specific protease 7 (USP7) has been reported to participate in a variety of cellular processes, including cell cycle, apoptosis, DNA damage response, and epigenetic modification. However, its function in preimplantation embryos is still obscure. To investigate the functions of USP7 during preimplantation embryo development, we used siRNA to degrade endogenous USP7 messenger RNA. We found that USP7 knockdown significantly decreased the development rate of mouse early embryos. Moreover, depletion of USP7 induced the accumulation of the DNA lesions and apoptotic blastomeres in early embryos. In addition, USP7 knockdown caused an abnormal H3K27me3 modification in 2-cell embryos. Overall, our results indicate that USP7 maintains genome stability perhaps via regulating H3K27me3 and DNA damage, consequently controlling the embryo quality.

摘要

作为泛素特异性蛋白酶亚家族的一员,泛素特异性蛋白酶 7(USP7)已被报道参与多种细胞过程,包括细胞周期、细胞凋亡、DNA 损伤反应和表观遗传修饰。然而,其在着床前胚胎中的功能尚不清楚。为了研究 USP7 在着床前胚胎发育过程中的作用,我们使用 siRNA 降解内源性 USP7 信使 RNA。我们发现,USP7 敲低显著降低了小鼠早期胚胎的发育速度。此外,USP7 的耗竭导致早期胚胎中 DNA 损伤和凋亡胚泡的积累。此外,USP7 敲低导致 2 细胞胚胎中 H3K27me3 修饰异常。总的来说,我们的结果表明,USP7 通过调节 H3K27me3 和 DNA 损伤来维持基因组稳定性,从而控制胚胎质量。

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USP7 reduction leads to developmental failure of mouse early embryos.USP7 缺失导致小鼠早期胚胎发育失败。
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FASEB J. 2020 Dec;34(12):16476-16488. doi: 10.1096/fj.202001875R. Epub 2020 Oct 23.

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Protein-targeting reverse genetic approaches: the future of oocyte and preimplantation embryo research.蛋白质靶向反向遗传学方法:卵母细胞和植入前胚胎研究的未来
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