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干细胞谱系中的可变剪接转换

Alternative splicing switching in stem cell lineages.

作者信息

Chepelev Iouri, Chen Xin

机构信息

Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.

出版信息

Front Biol (Beijing). 2013 Feb 1;8(1):50-59. doi: 10.1007/s11515-012-1198-y.

Abstract

The application of stem cells to regenerative medicine depends on a thorough understanding of the molecular mechanisms underlying their pluripotency. Many studies have identified key transcription factor-regulated transcriptional networks and chromatin landscapes of embryonic and a number of adult stem cells. In addition, recent publications have revealed another interesting molecular feature of stem cells- a distinct alternative splicing pattern. Thus, it is possible that both the identity and activity of stem cells are maintained by stem cell-specific mRNA isoforms, while switching to different isoforms ensures proper differentiation. In this review, we will discuss the generality of mRNA isoform switching and its interaction with other molecular mechanisms to regulate stem cell pluripotency, as well as the reprogramming process in which differentiated cells are induced to become pluripotent stem cell-like cells (iPSCs).

摘要

干细胞在再生医学中的应用依赖于对其多能性潜在分子机制的透彻理解。许多研究已经确定了胚胎干细胞和多种成体干细胞中关键转录因子调控的转录网络及染色质景观。此外,近期的出版物揭示了干细胞另一个有趣的分子特征——独特的可变剪接模式。因此,干细胞的特性和活性可能由干细胞特异性的mRNA异构体维持,而切换到不同的异构体则确保了适当的分化。在本综述中,我们将讨论mRNA异构体切换的普遍性及其与其他分子机制相互作用以调控干细胞多能性,以及将分化细胞诱导成为多能干细胞样细胞(诱导多能干细胞,iPSCs)的重编程过程。

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