Progesterone depletion results in Lamin B1 loss and induction of cell death in mouse trophoblast giant cells.

Progesterone depletion results in Lamin B1 loss and induction of cell death in mouse trophoblast giant cells.
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DOI:
10.1371/journal.pone.0254674
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Ogawa H
Ogawa H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Morimoto H;Ueno M;Tanabe H;Kono T;Ogawa H

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滋养层巨细胞(TGC)是一种小鼠滋养层亚型,具有大量的细胞质和通过内循环实现的高倍性水平。 TGC 的多种功能和基因表达谱已得到充分研究,但其核结构仍然未知。在本研究中,我们重点关注核纤层 Lamin B1,并阐明其表达动态、调控以及在 TGC 功能中的作用。使用从滋养层干细胞分化而来的 TGC。从分化后第0天到第9天,TGC的数量逐渐增加,但LMNB1的数量在第3天达到峰值,然后略有下降。免疫染色实验表明,分化第 6 天后,LMNB1 耗尽的 TGC 增加。这些 LMNB1 耗尽的 TGC 在细胞核中扩散了异染色质标记 H3K9me2 的外周定位。然而,LMINB1 敲低并不影响 TGC 特异性基因表达。我们发现分化第 6 天后 TGC 的死亡也增加。此外,Lamin B1 丢失和 TGC 中的细胞死亡受到 10−6 M 黄体酮的保护。我们的结果得出结论,黄体酮可防止 Lamin B1 丢失并延长 TGC 的寿命和功能。
Trophoblast giant cells (TGCs), a mouse trophoblast subtype, have large amounts of cytoplasm and high ploidy levels via endocycles. The diverse functions and gene expression profiles of TGCs have been studied well, but their nuclear structures remain unknown. In this study, we focus on Lamin B1, a nuclear lamina, and clarify its expression dynamics, regulation and roles in TGC functions. TGCs that differentiated from trophoblast stem cells were used. From days 0 to 9 after differentiation, the number of TGCs gradually increased, but the amount of LMNB1 peaked at day 3 and then slightly decreased. An immunostaining experiment showed that LMNB1-depleted TGCs increased after day 6 of differentiation. These LMNB1-depleted TGCs diffused peripheral localization of the heterochromatin marker H3K9me2 in the nuclei. However, LMINB1-knock down was not affected TGCs specific gene expression. We found that the death of TGCs also increased after day 6 of differentiation. Moreover, Lamin B1 loss and the cell death in TGCs were protected by 10−6 M progesterone. Our results conclude that progesterone protects against Lamin B1 loss and prolongs the life and function of TGCs.
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