Copper chaperone ATOX1 regulates pluripotency factor OCT4 in preimplantation mouse embryos

Copper chaperone ATOX1 regulates pluripotency factor OCT4 in preimplantation mouse embryos
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DOI:
10.1016/j.bbrc.2017.07.064
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发表时间:
2017-09-09
影响因子:
3.1
通讯作者:
Wittung-Stafshede, Pernilla
Wittung-Stafshede, Pernilla
中科院分区:
生物学4区
文献类型:
--
作者:
Celauro, Emanuele;Mukaj, Amisa;Wittung-Stafshede, Pernilla

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尽管铜在妊娠过程中很重要,但铜结合蛋白在早期胚胎发育中的作用尚不清楚。铜伴侣ATOX1最近被认为具有与转录和癌症相关的额外功能。当我们分析小鼠早期胚胎的单细胞RNA转录数据时,Atox1的转录水平在8细胞阶段急剧增加,在16和32细胞胚胎阶段,与Oct4的转录水平持平,Oct4在内细胞团中表达一种对多能性至关重要的转录因子。为了探索这一点,我们探索了Atox1在小鼠胚胎发育的第一周的表达。ATOX1在整个细胞中普遍表达,直到紧凑;在随后的胚胎阶段,ATOX1重新定位于内细胞团的胞质核周区域。沉默Oct4不影响Atoxl的表达,但在2-细胞期沉默Atoxl会显著降低16-细胞胚胎中Oct4的表达。(C)2017 Elsevier Inc.保留所有权利。
Despite of the importance of copper (Cu) during pregnancy, the roles of Cu-binding proteins during early embryonic development are unknown. The Cu chaperone ATOX1 was recently suggested to have additional functions related to transcription and cancer. When we analyzed single-cell RNA transcript data from early mouse embryos, Atox1 transcript levels increased dramatically at the 8-cell stage and, at 16 and 32-cell embryo stages, matched those of Oct4 which expresses a transcription factor essential for pluripotency in the inner cell mass. To explore this, we probed Atox1 expression during the first week of development of mouse embryos. ATOX1 appeared ubiquitously expressed throughout the cells until compaction; in subsequent embryo stages, ATOX1 relocalized to cytoplasmic perinuclear domains in the inner cell mass. Silencing of Oct4 did not affect Atoxl expression, but silencing of Atoxl at the 2-cell stage strongly diminished Oct4 expression in 16-cell embryos. (C) 2017 Elsevier Inc. All rights reserved.