Deciphering transcriptional regulation in human embryonic stem cells specified towards a trophoblast fate
Deciphering transcriptional regulation in human embryonic stem cells specified towards a trophoblast fate
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DOI：
10.1038/s41598-017-17614-5
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发表时间：
2017-12-08
影响因子：
4.6
通讯作者：
Tuteja, Geetu
中科院分区：
文献类型：
--
作者：
Jain, Ashish;Ezashi, Toshihiko;Tuteja, Geetu
分化的人胚胎干细胞（hESC）继续提供研究早期滋养层细胞（TB）的模型，但许多问题已经提出了关于他们的真实身份。因此，我们对先前发表的通过骨形态发生蛋白-4和激活素A和成纤维细胞生长因子-2信号传导抑制剂（BAP治疗）分化为TB的hESC的转录组学谱进行了全面和无偏倚的分析。我们的研究结果证实，BAP处理的hESC（ESCd）缺乏中胚层签名，是一种胎盘细胞亚型，与足月时存在的胎盘细胞不同。与常用的永生化TB细胞系和来自足月胎盘的原代细胞相比，ESCd显示出涉及迁移和侵袭的基因的高水平表达。共表达网络分析还确定了参与细胞迁移和粘附的基因模块，这些过程可能在胎盘形成的开始阶段至关重要。最后，蛋白质-蛋白质相互作用分析预测了其他几个可能在胎盘发育早期发挥重要作用的基因。总之，我们的分析提供了新的见解转录程序，活跃在ESCd。
Differentiated human embryonic stem cells (hESC) continue to provide a model for studying early trophoblast cells (TB), but many questions have been raised regarding their true identity. Therefore, we carried out a global and unbiased analysis on previously published transcriptomic profiles for hESC differentiated to TB by means of bone morphogenetic protein-4 and inhibitors of activin A and fibroblast growth factor-2 signaling (BAP treatment). Our results confirm that BAP treated hESC (ESCd) lack a mesoderm signature and are a subtype of placental cells unlike those present at term. ESCd display a high level of expression of genes implicated in migration and invasion compared to commonly used, immortalized TB cell lines and primary cells from term placenta. Co-expression network analysis also identified gene modules involved in cell migration and adhesion, processes that are likely critical during the beginning stages of placentation. Finally, protein-protein interaction analysis predicted several additional genes that may play important roles in early stages of placental development. Together, our analyses provide novel insights into the transcriptional programs that are active in ESCd.