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简明综述:诱导多能干细胞与胚胎干细胞:足够接近还是相差甚远?

Concise review: Induced pluripotent stem cells versus embryonic stem cells: close enough or yet too far apart?

机构信息

Center of Regenerative Medicine in Barcelona, Barcelona, Spain.

出版信息

Stem Cells. 2012 Jan;30(1):33-41. doi: 10.1002/stem.700.

Abstract

The state of a cell is defined by the genes it transcribes and the epigenetic landscape that regulates their expression. Pluripotent cells have markedly different epigenetic signatures when compared with differentiated cells. Permissive chromatin, high occurrence of bivalent domains, and low levels of heterochromatin allow pluripotent cells to react to distinctive stimuli and undergo changes of cell state by differentiating into various tissues. Differentiated cells can be reprogrammed by a set of transcription factors to induced pluripotent stem cells (iPSC) that convert their transcriptional and epigenetic state to pluripotency and thus closely resemble embryonic stem cells (ESC). However, questions remain on whether the epigenetic reprogramming is complete or if there are some recurring iPSC specific aberrations that impede their full pluripotency potential. For this reason, iPSC need to be closely compared with ESC, which is used as a golden standard for in vitro pluripotency. Transcribed genes, epigenetic landscape, differentiation potential, and mutational load show small but distinctive dissimilarities between these two cell types.

摘要

细胞的状态由其转录的基因和调节其表达的表观遗传景观定义。与分化细胞相比,多能细胞具有明显不同的表观遗传特征。允许性染色质、二价结构域的高发生率和异染色质的低水平允许多能细胞对独特的刺激作出反应,并通过分化为各种组织而发生细胞状态的变化。一组转录因子可以将分化细胞重新编程为诱导多能干细胞(iPSC),从而将其转录和表观遗传状态转化为多能性,因此与胚胎干细胞(ESC)非常相似。然而,仍然存在一些问题,即表观遗传重编程是否完全,或者是否存在一些反复出现的 iPSC 特异性异常,阻碍它们的完全多能性潜力。出于这个原因,需要将 iPSC 与 ESC 进行密切比较,ESC 被用作体外多能性的黄金标准。转录基因、表观遗传景观、分化潜力和突变负荷在这两种细胞类型之间表现出微小但明显的差异。

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