Jak1/Stat3 signaling acts as a positive regulator of pluripotency in chicken pre-gastrula embryos
Jak1/Stat3 signaling acts as a positive regulator of pluripotency in chicken pre-gastrula embryos
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DOI：
10.1016/j.ydbio.2016.11.001
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发表时间：
2017-01-01
影响因子：
2.7
通讯作者：
Agata, Kiyokazu
中科院分区：
文献类型：
--
作者：
Nakanoh, Shota;Fuse, Naoyuki;Agata, Kiyokazu
在发育的非常早期阶段出现的多能细胞是分化细胞的创始人。已经在小鼠中确定LIF/Jak/Stat-Nanog轴充当支持细胞的多能状态的正调节剂，而Fgf/Erk信号传导充当指导细胞进入分化状态的负调节剂。在鸡中，虽然已知Fgf/Erk信号传导作为负调节剂，但正调节剂仍然未知。在这里，为了鉴定鸡多能性的正调节因子，我们根据转录组分析选择Jak 1/Stat 3信号传导作为候选者。Jak 1/Stat 3信号在原肠胚形成前被特异性激活：Stat 3蛋白在胚盘期定位于细胞核，但在原肠胚形成后易位至细胞质。我们在胚盘衍生的集落形成试验中进行了药理学和基因转染分析，其中Nanog阳性密集集落代表了未分化状态的标志，并发现Jak 1/Stat 3信号支持鸡早期胚胎的多能性。Jak 1抑制消除了密集集落的形成，但当Stat 3 ER被人工激活时，殖民地形成得以恢复。我们认为，调节多能性的分子机制在小鼠和鸡之间的信号网络水平上是保守的，并且可能在更广泛的物种之间。
Pluripotent cells emerging at very early stages of development are the founders of differentiated cells. It has been established in mouse that the LIF/Jak/Stat-Nanog axis acts as a positive regulator to support the pluripotent state of cells whereas Fgf/Erk signaling acts as a negative regulator to direct cells to enter the differentiating state. In chicken, although Fgf/Erk signaling is known to act as a negative regulator, positive regulators remained unknown. Here, to identify positive regulator(s) of chicken pluripotency, we selected Jak1/ Stat3 signaling as a candidate based on transcriptome analyses. Jak1/Stat3 signaling was activated specifically at stages before gastrulation: Stat3 protein was localized in nuclei at blastodermal stages, but translocated to cytoplasm after gastrulation. We conducted pharmacological and gene transfection analyses in the blastoderm-derived colony formation assay, in which Nanog-positive dense colonies represent a hallmark of the undifferentiated state, and found that Jak1/Stat3 signaling supports pluripotency in chicken early embryos. Jak1 inhibition abolished the formation of dense colonies, but the colony formation was restored when Stat3ER was artificially activated. We propose that the molecular mechanisms regulating pluripotency are conserved at the signaling network level between mouse and chicken, and possibly among a wider range of species.