Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage
Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage
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DOI：
10.1016/j.stemcr.2016.01.009
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发表时间：
2016-03-08
影响因子：
5.9
通讯作者：
Sridharan, Rupa
中科院分区：
文献类型：
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作者：
Jackson, Steven A.;Olufs, Zachariah P. G.;Sridharan, Rupa
在小鼠胚胎成纤维细胞（MEF）重编程为诱导多能干细胞期间，多能性基因如NANOG的激活发生在间充质向上皮转化之后。在这里，我们报告说，成人干细胞（神经干细胞）和分化的细胞（星形胶质细胞）的神经谱系可以激活NANOG的钙粘蛋白表达的情况下，在重编程。基因表达分析显示，只有NANOG+ E-钙粘蛋白+群体表达稳定标志物，上调了几个细胞周期基因;并且是转基因独立的。DOT 1 L活性的抑制增强了神经干细胞中NANOG+和NANOG+E-cadherin+集落的数量。在重编程之前在MEFs中表达SOX 2不会改变表达E-钙粘蛋白的NANOG集落的比例。总之，这些结果为神经谱系细胞的重编程提供了独特的途径。
During the reprogramming of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells, the activation of pluripotency genes such as NANOG occurs after the mesenchymal to epithelial transition. Here we report that both adult stem cells (neural stem cells) and differentiated cells (astrocytes) of the neural lineage can activate NANOG in the absence of cadherin expression during reprogramming. Gene expression analysis revealed that only the NANOG+E-cadherin+ populations expressed stabilization markers, had upregulated several cell cycle genes; and were transgene independent. Inhibition of DOT1L activity enhanced both the numbers of NANOG+and NANOG+E-cadherin+ colonies in neural stem cells. Expressing SOX2 in MEFs prior to reprogramming did not alter the ratio of NANOG colonies that express E-cadherin. Taken together these results provide a unique pathway for reprogramming taken by cells of the neural lineage.