PDF(Pubmed)
Abstract：
Decidualization of the human endometrium is critical for establishing pregnancy and is entailed by differentiation of endometrial stromal cells (ESCs) into decidual cells. During decidualization, the actin cytoskeleton is dynamically reorganized for the ESCs\' morphological and functional changes. Although actin dynamically alters its polymerized state upon external stimuli not only in the cytoplasm, but also in the nucleus, nuclear actin dynamics during decidualization have not been elucidated. Here, we show that nuclear actin was specifically assembled during decidualization of human ESCs. This decidualization-specific formation of nuclear actin filaments was disassembled following the withdrawal of the decidualization stimulus, suggesting its reversible process. Mechanistically, RNA-seq analyses revealed that the forced disassembly of nuclear actin resulted in the suppression of decidualization, accompanied with the abnormal upregulation of cell proliferation genes, leading to incomplete cell cycle arrest. CCAAT/enhancer-binding protein beta (C/EBPβ), an important regulator for decidualization, was responsible for downregulation of the nuclear actin exporter, thus accelerating nuclear actin accumulation and its assembly for decidualization. Taken together, we demonstrate that decidualization-specific nuclear actin assembly induces cell cycle arrest for establishing the decidualized state of ESCs. We propose that not only the cytoplasmic actin, but also nuclear actin dynamics profoundly affect decidualization process in humans for ensuring pregnancy.
摘要：
人子宫内膜的蜕膜化对建立妊娠至关重要，并且需要子宫内膜基质细胞（ESC）分化为蜕膜细胞。在判定过程中，肌动蛋白细胞骨架动态重组为ESCs的形态和功能变化。尽管肌动蛋白不仅在细胞质中在外部刺激下动态地改变其聚合状态，而且在细胞核中，蜕膜化过程中的核肌动蛋白动力学尚未阐明。这里,我们表明，在人类ESC的蜕膜化过程中，核肌动蛋白是特异性组装的。蜕膜化刺激退出后，这种蜕膜化特异性形成的核肌动蛋白丝被分解，表明了它的可逆过程。机械上,RNA-seq分析显示，核肌动蛋白的强制分解导致蜕膜化的抑制，伴随着细胞增殖基因的异常上调，导致细胞周期停滞不完全。CCAAT/增强子结合蛋白β（C/EBPβ），决定化的重要调节器，负责下调核肌动蛋白出口国的监管，从而加速核肌动蛋白的积累和它的组装为蜕化作用。一起来看,我们证明了蜕膜化特异性核肌动蛋白组装诱导细胞周期停滞，以建立ESC的蜕膜化状态。我们认为，不仅细胞质肌动蛋白，而且核肌动蛋白动力学也深刻地影响人类的蜕膜化过程，以确保怀孕。
