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Skp2 contributes to cell cycle progression in trophoblast stem cells and to placental development.
Genes to Cells ( IF 1.3 ) Pub Date : 2020-04-08 , DOI: 10.1111/gtc.12769
Yuhei Yamauchi 1 , Akihiro Nita 1 , Masaaki Nishiyama 1 , Yoshiharu Muto 1 , Hideyuki Shimizu 1 , Hirokazu Nakatsumi 1 , Keiichi I Nakayama 1
Affiliation  

All trophoblast subtypes of the placenta are derived from trophoblast stem cells (TSCs). TSCs have the capacity to self‐renew, but how the proliferation of these cells is regulated in the undifferentiated state has been largely unclear. We now show that the F‐box protein Skp2 regulates the proliferation of TSCs and thereby plays a pivotal role in placental development in mice on the C57BL/6 background. The placenta of Skp2 −/− mouse embryos on the C57BL/6 background was smaller than that of their Skp2 +/+ littermates, with the mutant embryos also manifesting intrauterine growth retardation. Although the Skp2 −/− mice were born alive, most of them died before postnatal day 21, presumably as a result of placental defects. Depletion of Skp2 in TSCs cultured in the undifferentiated state resulted in a reduced rate of proliferation and arrest of the cell cycle in G1 phase, indicative of a defect in self‐renewal capacity. The cell cycle arrest apparent in Skp2‐deficient TSCs was reversed by additional ablation of the cyclin‐dependent kinase inhibitor (CKI) p57 but not by that of the CKI p27. Our results thus suggest that Skp2‐mediated degradation of p57 is an important determinant of the self‐renewal capacity of TSCs during placental development, at least in mice of certain genetic backgrounds.

中文翻译:

Skp2有助于滋养层干细胞的细胞周期进程和胎盘发育。

胎盘的所有滋养层亚型均来自滋养层干细胞(TSC)。TSC具有自我更新的能力,但是在未分化状态下如何调节这些细胞的增殖尚不清楚。现在,我们显示F框蛋白Skp2调节TSC的增殖,从而在C57BL / 6背景的小鼠胎盘发育中发挥关键作用。在C57BL / 6背景上,Skp2 -/-小鼠胚胎的胎盘比其Skp2 + / +同窝出生的小鼠的胎盘小,突变的胚胎也表现出宫内发育迟缓。虽然Skp2 -/-小鼠活着出生,其中大多数在出生后21天之前死亡,可能是由于胎盘缺陷所致。在未分化状态下培养的TSC中Skp2的耗竭导致增殖速率降低和G 1期细胞周期停滞,表明自我更新能力存在缺陷。进一步消融细胞周期蛋白依赖性激酶抑制剂(CKI)p57可逆转Skp2缺陷TSC中明显的细胞周期停滞,但不能被CKI p27消融。因此,我们的结果表明,至少在某些遗传背景的小鼠中,Skp2介导的p57降解是TSC在胎盘发育过程中自我更新能力的重要决定因素。
更新日期:2020-04-08
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