The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo.
The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo.
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DOI：
10.1242/dev.144139
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发表时间：
2017-04-15
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影响因子：
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通讯作者：
Zernicka-Goetz M
中科院分区：
文献类型：
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作者：
Goolam M;Zernicka-Goetz M
内细胞团内的胚胎与胚胎外组织分离，产生外胚层（EPI），外胚层（EPI）将形成新的生物体，而原始内胚层（PE）将形成卵黄囊，这是一个至关重要的发育决定。在这里，我们确定了一个染色质修饰剂 Satb1，在这个决定中发挥着独特的作用。 Satb1 在 16 细胞阶段胚胎中差异表达，在内细胞团祖细胞中表达水平较高。耗尽 Satb1 会增加 EPI 细胞的数量，但会损害 PE。由于 Satb1 和 Satb2 对多能性调节因子 Nanog 的拮抗作用，可以通过同时耗尽 Satb1 和 Satb2 来挽救这种表型。因此，Satb1 表达的增加会导致分化为 PE 并降低 EPI，这是 Satb1 调节多个多能性和分化相关基因表达的结果。最后，我们证明 Satb1 是 Fgf 信号通路的下游靶标，连接染色质修饰和 Fgf 信号传导。总之，这些结果确定了 Satb1 在多能性和分化之间的谱系选择中的作用，并进一步加深了我们对早期胚胎谱系分离的理解。摘要： Satb1 调节早期小鼠胚胎中多能性和分化之间的细胞命运选择，是 Fgf 信号通路的下游靶标。
The separation of embryonic from extra-embryonic tissues within the inner cell mass to generate the epiblast (EPI), which will form the new organism, from the primitive endoderm (PE), which will form the yolk sac, is a crucial developmental decision. Here, we identify a chromatin modifier, Satb1, with a distinct role in this decision. Satb1 is differentially expressed within 16-cell-stage embryos, with higher expression levels in the inner cell mass progenitor cells. Depleting Satb1 increases the number of EPI cells at the expense of PE. This phenotype can be rescued by simultaneous depletion of both Satb1 and Satb2, owing to their antagonistic effect on the pluripotency regulator Nanog. Consequently, increasing Satb1 expression leads to differentiation into PE and a decrease in EPI, as a result of the modulation of expression of several pluripotency- and differentiation-related genes by Satb1. Finally, we show that Satb1 is a downstream target of the Fgf signalling pathway, linking chromatin modification and Fgf signalling. Together, these results identify a role for Satb1 in the lineage choice between pluripotency and differentiation and further our understanding of early embryonic lineage segregation. Summary: Satb1 regulates the cell fate choice between pluripotency and differentiation in the early mouse embryo and is a downstream target of the Fgf signalling pathway.