Foxd3 suppresses NFAT‐mediated differentiation to maintain self‐renewal of embryonic stem cells
Foxd3 suppresses NFAT‐mediated differentiation to maintain self‐renewal of embryonic stem cells
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DOI：
10.15252/embr.201438643
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发表时间：
2014-12
期刊：
影响因子：
7.7
通讯作者：
Lili Zhu;Shiyue Zhang;Ying Jin
中科院分区：
文献类型：
--
作者：
Lili Zhu;Shiyue Zhang;Ying Jin
多能性相关转录因子Foxd 3是维持多能细胞所必需的。然而，其功能的分子机制在很大程度上是未知的。在这里，我们报告说，Foxd 3抑制钙调神经磷酸酶-NFAT信号诱导的分化，以维持ESC的身份。在机制上，Foxd 3与NFAT蛋白相互作用，并招募共阻遏物Tle 4（在未分化的ESC中高度表达的Tle阻遏物家族的成员）来抑制NFATc 3的转录活性。此外，全局转录组分析表明，Foxd 3和NFATc 3共调节ESC中的一组分化相关基因。总的来说，我们的研究建立了多能性相关因子和重要的ESC分化诱导途径之间的分子和功能联系。
Pluripotency‐associated transcription factor Foxd3 is required for maintaining pluripotent cells. However, molecular mechanisms underlying its function are largely unknown. Here, we report that Foxd3 suppresses differentiation induced by calcineurin–NFAT signaling to maintain the ESC identity. Mechanistically, Foxd3 interacts with NFAT proteins and recruits co‐repressor Tle4, a member of the Tle repressor family highly expressed in undifferentiated ESCs, to suppress NFATc3's transcriptional activities. Furthermore, global transcriptome analysis shows that Foxd3 and NFATc3 co‐regulate a set of differentiation‐associated genes in ESCs. Collectively, our study establishes a molecular and functional link between a pluripotency‐associated factor and an important ESC differentiation‐inducing pathway.