Embryonic stem cells induce pluripotency in somatic cell fusion through biphasic reprogramming.
Embryonic stem cells induce pluripotency in somatic cell fusion through biphasic reprogramming.
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胚胎干细胞通过双相重编程在体细胞融合中诱导多能性。
DOI：
10.1016/j.molcel.2012.02.013
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发表时间：
2012-04-27
期刊：
影响因子：
16
通讯作者：
Lahn BT
中科院分区：
文献类型：
--
作者：
Foshay KM;Looney TJ;Chari S;Mao FF;Lee JH;Zhang L;Fernandes CJ;Baker SW;Clift KL;Gaetz J;Di CG;Xiang AP;Lahn BT
细胞融合重编程基因表达是一个长期存在的范式，但重编程的程度以及它是否受到所用细胞类型的影响仍然未知。我们最近发现，体细胞基因的沉默是由于反式作用的细胞环境或顺式作用的染色质上下文。在这里，我们研究如何反式与顺式沉默基因的体细胞类型的行为融合到另一个体细胞类型或胚胎干细胞（ESC）。我们证明，虽然反式沉默体细胞基因的重编程发生在这两种类型的融合中，但顺式沉默体细胞基因的重编程仅发生在体细胞-ESC融合中。重要的是，胚胎干细胞在两个不同的阶段重编程体细胞基因组：反式重编程发生迅速独立的DNA复制，而顺式重编程发生缓慢的动力学需要DNA复制。我们还表明，多能性基因Oct 4和Nanog是顺式沉默体细胞。我们的结论是顺式重编程能力是区分胚胎干细胞从体细胞的一个基本特征。
It is a long-held paradigm that cell fusion reprograms gene expression, but the extent of reprogramming and whether it is affected by the cell types employed remain unknown. We recently showed that the silencing of somatic genes is attributable to either trans-acting cellular environment or cis-acting chromatin context. Here, we examine how trans- versus cis-silenced genes in a somatic cell type behave in fusions to another somatic cell type or to embryonic stem cells (ESCs). We demonstrate that while reprogramming of trans-silenced somatic genes occurs in both types of fusions, reprogramming of cis-silenced somatic genes occurs only in somatic-ESC fusions. Importantly, ESCs reprogram somatic genome in two distinct phases: trans-reprogramming occurs rapidly independent of DNA replication, whereas cis-reprogramming occurs with slow kinetics requiring DNA replication. We also show that pluripotency genes Oct4 and Nanog are cis-silenced in somatic cells. We conclude that cis-reprogramming capacity is a fundamental feature distinguishing ESCs from somatic cells.