Foxd1 is a mediator and indicator of the cell reprogramming process
Foxd1 is a mediator and indicator of the cell reprogramming process
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DOI：
10.1038/ncomms4197
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发表时间：
2014-02-01
影响因子：
16.6
通讯作者：
Ebisuya, Miki
中科院分区：
文献类型：
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作者：
Koga, Makito;Matsuda, Mitsuhiro;Ebisuya, Miki
目前尚不清楚在细胞重新编程过程中，建立多潜能状态的基因表达谱是如何产生变化的。在这里，我们确定了两个叉头盒转录因子，Foxd1和Foxo1，作为重编程过程中基因表达程序变化的中介。Foxd1或Foxo1的敲除会减少ipscs的数量，而双重敲除则会进一步减少。Foxd1的敲除抑制下游转录事件，包括Dax1的表达，Dax1是维持多能性的自动调节网络的组成部分。有趣的是，在重新编程的中期，Foxd1的表达水平在一小部分细胞中瞬时增加。Foxd1在这一阶段的瞬时上调与未来细胞的IPSCs命运相关。命运图谱分析进一步表明，95%的IPSC克隆来自Foxd1阳性细胞。因此，Foxd1是重新编程成功进展的调节因子和指示器。
It remains unclear how changes in gene expression profiles that establish a pluripotent state are induced during cell reprogramming. Here we identify two forkhead box transcription factors, Foxd1 and Foxo1, as mediators of gene expression programme changes during reprogramming. Knockdown of Foxd1 or Foxo1 reduces the number of iPSCs, and the double knockdown further reduces it. Knockout of Foxd1 inhibits downstream transcriptional events, including the expression of Dax1, a component of the autoregulatory network for maintaining pluripotency. Interestingly, the expression level of Foxd1 is transiently increased in a small population of cells in the middle stage of reprogramming. The transient Foxd1 upregulation in this stage is correlated with a future cell fate as iPSCs. Fate mapping analyses further reveal that >95% of iPSC colonies are derived from the Foxd1-positive cells. Thus, Foxd1 is a mediator and indicator of successful progression of reprogramming.