T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications
T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications
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DOI：
10.1073/pnas.1017402108
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发表时间：
2011-07-19
影响因子：
11.1
通讯作者：
Pia Cosma, Maria
中科院分区：
文献类型：
--
作者：
Lluis, Frederic;Ombrato, Luigi;Pia Cosma, Maria
必须克服异染色质屏障才能产生诱导多能干细胞和细胞融合介导的重编程杂交体。在这里，我们发现，T 细胞因子 3 (Tcf3)（β-连环蛋白靶基因的抑制因子）的缺失，可以显着且快速地提高神经前体细胞 (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，并且可以在融合后极大地重新编程NPC。此外，在将 NPC 重新编程为诱导多能干细胞的过程中，在内源干细胞基因重新激活之前和很久之前，Tcf3 的沉默会增加 AcH3 并减少 H3K9me3 阳性异染色质灶的数量。总之，我们的数据表明 Tcf3 充当体细胞重编程潜力的阻遏物。
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 beta-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.