MicroRNA-20b and ERK1/2 pathway independently regulate the expression of tissue factor in hematopoietic and trophoblastic differentiation of human embryonic stem cells.
MicroRNA-20b and ERK1/2 pathway independently regulate the expression of tissue factor in hematopoietic and trophoblastic differentiation of human embryonic stem cells.
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MicroRNA-20b和ERK1/2通路独立调控人胚胎干细胞造血和滋养层分化中组织因子的表达
DOI：
10.1186/scrt332
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发表时间：
2013-10-11
影响因子：
7.5
通讯作者：
Chen FP
中科院分区：
文献类型：
--
作者：
Yu YH;Wu DS;Huang FF;Zhang Z;Liu LX;Zhang J;Zhan HE;Peng MY;Zeng H;Chen FP
组织因子（TF）在各种类型的细胞中表达。TF的表达对许多生物过程至关重要，如血液凝固和胚胎发育，而其在干细胞中的高表达往往导致移植失败。在这项研究中，我们利用人胚胎干细胞（hESC）培养系统来了解TF在hESC来源的造血和滋养细胞中表达调控的分子机制。方法体外诱导干细胞分化为造血细胞和滋养细胞。通过实时定量聚合酶链反应和western blot分析检测不同类型细胞在这些分化过程中的TF表达。通过miRNA表达分析、荧光素酶报告分析、TF mRNA和蛋白分析以及通路磷酸化分析来研究TF表达的调控机制。结果首先发现TF仅在造血干细胞分化的滋养细胞和粒细胞单核细胞（G-M）中表达；然后证明miR-20b下调，Erk1/2信号通路上调滋养层细胞和G-M细胞中TF的表达。最后，我们发现miR-20b可以独立于Erk1/2信号通路下调TF的表达。结论miR-20b和Erk1/2通路独立调控造血干细胞分化的滋养细胞和G-M细胞中TF的表达。这些发现将为进一步阐明TF在各种生物过程中的功能开辟一条途径。
IntroductionTissue factor (TF) is expressed in various types of cells. TF expression is essential for many biological processes, such as blood coagulation and embryonic development, while its high expression in stem cells often leads to failure of transplantation. In this study, we used the human embryonic stem cell (hESC) culture system to understand the molecular mechanisms by which TF expression is regulated in hESC-derived hematopoietic and trophoblastic cells.MethodshESCs were inducedin vitroto differentiate into hematopoietic and trophoblastic cells. TF expression in various types of cells during these differentiation processes was examined by quantitative real-time polymerase chain reaction analysis and western blot analysis. The regulatory mechanisms of TF expression were investigated by miRNA expression analysis, luciferase report assay, TF mRNA and protein analysis, and pathway phosphorylation analysis.ResultsWe first found that TF was expressed only in trophoblasts and granulocyte–monocyte (G-M) cells differentiated from hESCs; and then demonstrated that miR-20b downregulated and Erk1/2 signaling pathway upregulated the TF expression in trophoblasts and G-M cells. Finally, we found that miR-20b downregulated the TF expression independently of the Erk1/2 signaling pathway.ConclusionsThe miR-20b and Erk1/2 pathway independently regulate expression of TF in trophoblasts and G-M cells differentiated from hESCs. These findings will open an avenue to further illustrate the functions of TF in various biological processes.
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