Calcineurin‐NFAT Signaling Controls Somatic Cell Reprogramming in a Stage‐Dependent Manner
Calcineurin‐NFAT Signaling Controls Somatic Cell Reprogramming in a Stage‐Dependent Manner
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DOI：
10.1002/jcp.25212
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发表时间：
2016-05
影响因子：
5.6
通讯作者：
Ming Sun;Bing Liao;Yu Tao;Hao Chen;Feng Xiao;J. Gu;Shaorong Gao;Ying Jin
中科院分区：
文献类型：
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作者：
Ming Sun;Bing Liao;Yu Tao;Hao Chen;Feng Xiao;J. Gu;Shaorong Gao;Ying Jin
钙调神经磷酸酶-NFAT信号对小鼠胚胎干细胞和早期胚胎的早期谱系确定至关重要。然而，它在体细胞重编程中的作用仍不清楚。在这里，我们报道了钙调神经磷酸酶-NFAT信号具有动态的活性，并在重编程的不同阶段扮演不同的角色。在早期阶段，钙调神经磷酸酶-NFAT信号被瞬时激活，它的激活是成功重新编程所必需的。然而，在重编程的后期，钙调神经磷酸酶-NFAT信号的激活成为重编程的障碍，其失活是成功诱导多能性的关键。从机制上讲，钙调神经磷酸酶-NFAT信号通过调节重编程过程中的多个早期事件参与重编程，包括间充质向上皮细胞的转变(MET)、细胞黏附和SSEA1+中间细胞的出现。总之，本研究首次揭示了钙调神经磷酸酶-NFAT信号在体细胞重编程中的重要作用，并为重编程的分子调控提供了新的见解。J.细胞。物理。231：1151-1162,2016。©2015 Wiley期刊，Inc.
Calcineurin‐NFAT signaling is critical for early lineage specification of mouse embryonic stem cells and early embryos. However, its roles in somatic cell reprogramming remain unknown. Here, we report that calcineurin‐NFAT signaling has a dynamic activity and plays diverse roles at different stages of reprogramming. At the early stage, calcineurin‐NFAT signaling is transiently activated and its activation is required for successful reprogramming. However, at the late stage of reprogramming, activation of calcineurin‐NFAT signaling becomes a barrier for reprogramming and its inactivation is critical for successful induction of pluripotency. Mechanistically, calcineurin‐NFAT signaling contributes to the reprogramming through regulating multiple early events during reprogramming, including mesenchymal to epithelial transition (MET), cell adhesion and emergence of SSEA1+ intermediate cells. Collectively, this study reveals for the first time the important roles of calcineurin‐NFAT signaling during somatic cell reprogramming and provides new insights into the molecular regulation of reprogramming. J. Cell. Physiol. 231: 1151–1162, 2016. © 2015 Wiley Periodicals, Inc.