NPTX1 Regulates Neural Lineage Specification from Human Pluripotent Stem Cells (Retracted Article)
NPTX1 Regulates Neural Lineage Specification from Human Pluripotent Stem Cells (Retracted Article)
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DOI：
10.1016/j.celrep.2014.01.026
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发表时间：
2014-02-01
期刊：
影响因子：
8.8
通讯作者：
Fasano, Christopher A.
中科院分区：
文献类型：
--
作者：
Boles, Nathan C.;Hirsch, Sarah E.;Fasano, Christopher A.
神经诱导是神经系统形成的第一个基本步骤。在发育过程中，一个严格调控的生态位调节短暂的细胞外信号来影响神经谱系的承诺。然而，到目前为止，维持人类这些信号的分子事件级联还没有得到很好的理解。在这里，我们发现NPTX1，一种分泌蛋白，在人类多能干细胞（hPSCs）的神经诱导过程中迅速上调。通过操纵它的表达，我们能够减少或启动神经谱系的承诺。时间过程转录组分析和功能分析表明，NPTX1部分通过结合节点受体辅助因子TDGF1起作用，减少节点和BMP信号。我们的发现确定了最早的基因表达的神经诱导和提供洞察人类神经谱系规范。
Neural induction is the first fundamental step in nervous system formation. During development, a tightly regulated niche modulates transient extracellular signals to influence neural lineagecommitment. To date, however, the cascade of molecular events that sustain these signals in humans is not well understood. Here we show that NPTX1, a secreted protein, is rapidly upregulated during neural induction from human pluripotent stem cells (hPSCs). By manipulating its expression, we were able to reduce or initiate neural lineagecommitment. Atime-course transcriptome analysis and functional assays show that NPTX1 acts in part by binding the Nodal receptor cofactor TDGF1, reducing both Nodal and BMP signaling. Our findings identify one of the earliest genes expressed upon neural induction and provide insight into human neural lineage specification.