Hyperthermia depletes Oct4 in mouse blastocysts and stem cells

Hyperthermia depletes Oct4 in mouse blastocysts and stem cells
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高温会消耗小鼠囊胚和干细胞中的 Oct4

DOI:
10.1186/s13287-020-01715-6
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发表时间:
2020-05
影响因子:
7.5
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学2区
文献类型:
--
作者:
Cheng M.B.;Wang X;Huang Y;Zhang Y

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温度是在正常胚胎发育中发挥表观遗传作用的重要微环境因素。然而,热疗对干细胞的影响尚不完全清楚。 Oct4 是干细胞和早期胚胎发育过程中多能性维持的严格调控的主调节因子。我们在此报道,在小鼠囊胚和胚胎干细胞的高温下,Oct4 蛋白水平显着降低。高温下小鼠胚胎干细胞中 Oct4 的减少是由泛素蛋白酶体途径介导的,该途径依赖于死亡相关蛋白激酶 1 (Dapk1) 磷酸化其底物 Pin1 的活性。我们的结果表明,怀孕早期通过短暂的高热(例如高烧)导致的 Oct4 消耗可能会严重损害哺乳动物胚胎的生长,甚至导致其死亡。
Temperature is an important microenvironmental factor that functions epigenetically in normal embryonic development. However, the effect of hyperthermia in the stem cells is not fully understood. Oct4 is a tightly regulated master regulator of pluripotency maintenance in stem cells and during early embryonic development. We report here that Oct4 protein level was significantly reduced under hyperthermia in mouse blastocysts and embryonic stem cells. The reduction in Oct4 in the mouse embryonic stem cells under hyperthermia was mediated by a ubiquitin-proteasome pathway that was dependent on the activity of death-associated protein kinase 1 (Dapk1) to phosphorylate its substrate, Pin1. Our results imply that the depletion of Oct4 via brief hyperthermia, such as a high fever, during early pregnancy might severely impair the growth of the mammalian embryo or even cause its death.
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