Centre de Regulació Genòmica, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11912-7. doi: 10.1073/pnas.1017402108. Epub 2011 Jul 5.
The heterochromatin barrier must be overcome to generate induced pluripotent stem cells and cell fusion-mediated reprogrammed hybrids. Here, we show that the absence of T-cell factor 3 (Tcf3), a repressor of β-catenin target genes, strikingly and rapidly enhances the efficiency of neural precursor cell (NPC) reprogramming. Remarkably, Tcf3(-/-) ES cells showed a genome-wide increase in AcH3 and decrease in H3K9me3 and can reprogram NPCs after fusion greatly. In addition, during reprogramming of NPCs into induced pluripotent stem cells, the silencing of Tcf3 increased AcH3 and decreased the number of H3K9me3-positive heterochromatin foci early and long before reactivation of the endogenous stem cell genes. In conclusion, our data suggest that Tcf3 functions as a repressor of the reprogramming potential of somatic cells.
异染色质屏障必须被克服，才能产生诱导多能干细胞和细胞融合介导的重编程杂种。在这里，我们表明，缺乏 T 细胞因子 3（Tcf3），β-catenin 靶基因的抑制剂，显著且迅速地提高了神经前体细胞（NPC）重编程的效率。值得注意的是，Tcf3（-/-）ES 细胞显示出全基因组范围内 AcH3 的增加和 H3K9me3 的减少，并能在融合后极大地重编程 NPC。此外，在 NPC 重编程为诱导多能干细胞期间，Tcf3 的沉默在重新激活内源性干细胞基因之前很早就增加了 AcH3，并减少了 H3K9me3 阳性异染色质焦点的数量。总之，我们的数据表明 Tcf3 作为体细胞重编程潜力的抑制剂发挥作用。
