Activation of Blood Vessel Development in Endometrial Stromal Cells In Vitro Cocultured with Human Peri-Implantation Embryos Revealed by Single-Cell RNA-Seq.

Activation of Blood Vessel Development in Endometrial Stromal Cells In Vitro Cocultured with Human Peri-Implantation Embryos Revealed by Single-Cell RNA-Seq.
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单细胞 RNA 测序揭示子宫内膜基质细胞与人类围着床胚胎体外共培养血管发育的激活

DOI:
10.3390/life11050367
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发表时间:
2021-04-21
期刊:
Life (Basel, Switzerland)
影响因子:
--
通讯作者:
Xue Z
Xue Z
中科院分区:
其他
文献类型:
--
作者:
Lv B;Xu X;Zhang X;Qi L;He W;Wang L;Chen X;Peng L;Xue J;Ji Y;Xue Z

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在人类中,母体子宫内膜参与与囊胚的物理和生理相互作用,开始着床。双向串音对正常着床和成功妊娠至关重要。虽然有几项研究使用动物模型或细胞系来研究这一步骤,但很少有人了解子宫内膜细胞在人类中的作用。在这里,我们分析了来自先前研究的单细胞测序数据,包括24个未共培养的子宫内膜基质细胞(EmSCs)和57个与胚胎共培养的EmSCs。我们进一步探讨了共培养后EmSCs的转录组变化及其与滋养细胞的相互作用。差异表达基因(DEG)分析显示共培养胚中有1783个上调基因和569个下调基因。这些deg的体重基因共表达网络和基因本体分析显示,共培养后的EmSCs中RAMP1、LTBP1和LRP1的表达量较高,表明血管发育和女性妊娠的生物学过程富集。这些数据表明,EmSCs在植入阶段就开始了血管发育。与植入窗口的子宫内膜数据相比,这一阶段涉及上皮细胞发育和氧反应等关键途径。利用CellphoneDB进行的进一步分析揭示了EmSCs与胚胎滋养层细胞之间的相互作用,表明整合素和成纤维细胞生长因子途径在植入过程中发挥了重要作用。综上所述,我们的工作揭示了在植入阶段发生的同步信号和途径,涉及EmSCs的接受性获得以及EmSCs与滋养细胞之间的相互作用。
In humans, the maternal endometrium participates in the physical and physiological interaction with the blastocyst to begin implantation. A bidirectional crosstalk is critical for normal implantation and then a successful pregnancy. While several studies have used animal models or cell lines to study this step, little knowledge was acquired to address the role of endometrial cells in humans. Here, we analyzed single-cell sequencing data from a previous study including 24 non-coculture endometrial stromal cells (EmSCs) and 57 EmSCs after coculture with embryos. We further explored the transcriptomic changes in EmSCs and their interactions with trophoblast cells after coculture. Differentially expressed gene (DEG) analysis showed 1783 upregulated genes and 569 downregulated genes in the cocultured embryos. Weight gene coexpression network and gene ontology analysis of these DEGs showed a higher expression of RAMP1, LTBP1, and LRP1 in EmSCs after coculture, indicating the enrichment of biological processes in blood vessel development and female pregnancy. These data imply that EmSCs start blood vessel development at the implantation stage. Compared with endometrium data in vivo at the implantation window, key pathways including epithelial cell development and oxygen response were involved at this stage. Further analysis using CellphoneDB shed light on the interactions between EmSCs and embryonic trophoblasts, suggesting the important role of integrins and fibroblast growth factor pathways during implantation. Taken together, our work reveals the synchronization signaling and pathways happening at the implantation stage involving the acquisition of receptivity in EmSCs and the interaction between EmSCs and trophoblast cells.
DOI: 10.1038/ncb3347
发表时间: 2016-06
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发表时间: 2016-05-12
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影响因子: 64.8
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