CITED2 modulation of trophoblast cell differentiation: insights from global transcriptome analysis.
CITED2 modulation of trophoblast cell differentiation: insights from global transcriptome analysis.
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DOI：
10.1530/rep-15-0555
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Soares MJ
中科院分区：
文献类型：
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作者：
Imakawa K;Dhakal P;Kubota K;Kusama K;Chakraborty D;Karim Rumi MA;Soares MJ
滋养层干细胞 (TS) 具有沿着多谱系途径分化产生多种特殊细胞类型的能力。人们对控制滋养层细胞分化的调控网络知之甚少。 cAMP 反应元件结合蛋白/p300 相互作用反式激活因子与富含 Glu/Asp 的羧基末端结构域 2 (CITED2) 与胎盘形成的调节有关；然而，我们对 CITED2 如何影响滋养层细胞知之甚少。大鼠 Rcho-1 滋养层干 (TS) 细胞可进行增殖或分化为专门的滋养层谱系，是研究滋养层分化的绝佳模型。 CITED2 转录物和蛋白质在 Rcho-1 TS 细胞分化过程中显示出强烈的诱导作用。我们使用短发夹 RNA 敲低方法来破坏 CITED2 表达，以研究其在滋养层细胞分化中的作用。 RNA 测序用于检查 CITED2 对滋养层细胞分化的影响。 CITED2 破坏影响分化的滋养层细胞转录组。 CITED2 在细胞分化调节中发挥着重要作用，与多种信号转导途径以及缺氧调节和凝血过程有关。总之，我们的研究结果表明 CITED2 有助于调节滋养层细胞分化。
Trophoblast stem (TS) cells possess the capacity to differentiate along a multi-lineage pathway yielding several specialized cell types. The regulatory network controlling trophoblast cell differentiation is poorly understood. cAMP-response element binding protein/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain-2 (CITED2) has been implicated in the regulation of placentation; however, we know little about how CITED2 acts to influence trophoblast cells. Rat Rcho-1 trophoblast stem (TS) cells can be manipulated to proliferate or differentiate into specialized trophoblast lineages and are an excellent model for investigating trophoblast differentiation. CITED2 transcript and protein showed a robust induction during Rcho-1 TS cell differentiation. We used a short hairpin RNA knockdown approach to disrupt CITED2 expression in order to investigate its involvement in trophoblast cell differentiation. RNA-sequencing was used to examine the impact of CITED2 on trophoblast cell differentiation. CITED2 disruption affected the differentiating trophoblast cell transcriptome. CITED2 possessed a prominent role in the regulation of cell differentiation with links to several signal transduction pathways and to hypoxia-regulated and coagulation processes. In summary, our findings indicate that CITED2 contributes to the regulation of trophoblast cell differentiation.