Blastocyst activation engenders transcriptome reprogram affecting X-chromosome reactivation and inflammatory trigger of implantation
Blastocyst activation engenders transcriptome reprogram affecting X-chromosome reactivation and inflammatory trigger of implantation
复制标题
囊胚激活引起转录组重编程，影响 X 染色体重新激活和植入的炎症触发
DOI：
10.1073/pnas.1900401116
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发表时间：
2019-08-13
影响因子：
11.1
通讯作者：
Kong, Shuangbo
中科院分区：
文献类型：
--
作者：
He, Bo;Zhang, Hangxiao;Kong, Shuangbo
意义我们的数据系统和全面地揭示了胚泡在延迟着床小鼠模型中植入的遗传程序。通过对转录谱的分析，我们展示了滞育后囊胚重新激活过程中生物合成、代谢和细胞增殖的动态变化。我们分别分析了ICM和TE的整体重构，并揭示了植入过程中的关键细胞和分子事件。此外，我们的结果表明，激活的胚泡作为促炎性小体发挥作用，以触发类似炎症的附着反应。因此，我们展示了胚泡在着床过程中以前未明确的作用。我们认为，这项研究的发现极大地促进了对植入过程中炎症-附着反应的科学理解。胚泡植入子宫是哺乳动物进一步胚胎发育的门户。将胚泡编程到能着床的状态，即胚泡激活，是着床至受精子宫的决定性因素。然而，很大程度上仍不清楚胚泡是如何在全球范围内编程植入的。利用延迟着床小鼠模型，我们在这里展示了胚泡经历了着床所必需的广泛的编程。通过分析不同着床能力的囊胚的转录谱，我们揭示了滞育后囊胚再激活过程中生物合成、代谢和增殖的动态变化。我们还证明，X染色体的重新激活是女性胚胎发育围着床期最重要的事件之一，尽管在子宫中长期悬浮，但即使在休眠条件下的囊胚中，X染色体的重新激活也没有完成。此外，壁状滋养外胚层(TE)，而不是极滋养外胚层，通过减弱的细胞-细胞紧密连接和细胞外基质(ECM)分化为更具侵袭性。通过分析分泌蛋白的差异表达谱，我们进一步证明了胚泡作为促炎小体分泌促炎信号，如肿瘤坏死因子α和S100A9，从而在着床过程中触发胚胎-子宫附着反应。总而言之，我们的数据系统和全面地揭示了胚泡从滞育重新激活到着床的程序，并揭示了胚泡在着床过程中先前未明确的角色。
Significance Our data systematically and comprehensively reveal the genetic programming of blastocyst for implantation in a delayed implantation mouse model. By analyzing the transcriptional profile, we demonstrate dynamic changes in the biosynthesis, metabolism, and cell proliferation during blastocyst reactivation from diapause. We have analyzed the global remodeling of ICM and TE, respectively, and disclosed the critical cellular and molecular events during implantation. Furthermore, our results suggest that an activating blastocyst functions as a proinflammatory body to trigger an inflammatory-like attachment response. Thus, we demonstrate a previously undefined role of blastocyst during implantation. We believe that the findings in this study substantially advance scientific understanding of the inflammatory-attachment response during implantation. Implantation of the blastocyst into the uterus is the gateway for further embryonic development in mammals. Programming of blastocyst to an implantation-competent state known as blastocyst activation is the determining factor for implantation into the receptive uterus. However, it remains largely unclear how the blastocyst is globally programmed for implantation. Employing a delayed implantation mouse model, we show here that the blastocyst undergoes extensive programming essential for implantation. By analyzing the transcriptional profile of blastocysts with different implantation competency, we reveal the dynamic change in the biosynthesis, metabolism, and proliferation during blastocyst reactivation from diapause. We also demonstrate that reactivation of the X chromosome, one of the most important events during periimplantation of female embryonic development, is not completed even in blastocysts under conditions of dormancy, despite long term suspension in the uterus. Moreover, the mural trophectoderm (TE), but not the polar TE, differentiates to be more invasive through the weakened cell-cell tight junctions and extracellular matrices (ECMs). By analyzing the differentially expressed profile of secretory proteins, we further demonstrate that the blastocyst functions as a proinflammatory body to secrete proinflammatory signals, such as TNFα and S100A9, thereby triggering embryo-uterine attachment reaction during implantation. Collectively, our data systematically and comprehensively disclose the programming of blastocyst reactivation from diapause for implantation and uncover previously undefined roles of blastocyst during implantation.