Jackson Steven A, Olufs Zachariah P G, Tran Khoa A, Zaidan Nur Zafirah, Sridharan Rupa
Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA.
Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin, 1111 Highland Avenue, Madison, WI 53715, USA.
Stem Cell Reports. 2016 Mar 8;6(3):302-11. doi: 10.1016/j.stemcr.2016.01.009. Epub 2016 Feb 18.
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.
在将小鼠胚胎成纤维细胞（MEFs）重编程为诱导多能干细胞的过程中，多能性基因如NANOG的激活发生在间充质向上皮转变之后。在此我们报告，神经谱系的成体干细胞（神经干细胞）和分化细胞（星形胶质细胞）在重编程过程中，在缺乏钙黏蛋白表达的情况下均可激活NANOG。基因表达分析显示，只有NANOG+E-钙黏蛋白+群体表达稳定标记，上调了多个细胞周期基因；并且不依赖转基因。抑制DOT1L活性可增加神经干细胞中NANOG+和NANOG+E-钙黏蛋白+集落的数量。在重编程之前在MEFs中表达SOX2不会改变表达E-钙黏蛋白的NANOG集落的比例。综上所述，这些结果为神经谱系细胞的重编程提供了一条独特的途径。
