A general strategy for cellular reprogramming: The importance of transcription factor cross-repression
A general strategy for cellular reprogramming: The importance of transcription factor cross-repression
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DOI：
10.1002/stem.1473
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发表时间：
2013-10-01
期刊：
影响因子：
5.2
通讯作者：
del Sol, Antonio
中科院分区：
文献类型：
--
作者：
Crespo, Isaac;del Sol, Antonio
转录因子交叉抑制是细胞分化中的一个重要概念。双稳态触发开关构成了决定细胞承诺的分子机制，并为二元细胞命运选择的转录程序提供了稳定性。实验支持，这些触发开关的扰动可以相互转换这些二进制单元的命运选择，这暗示了潜在的重新编程策略。然而，更复杂类型的细胞转变可能涉及不同类型的多稳定基序组合的扰动。在这里，我们介绍了一种方法，该方法推广了转录因子交叉抑制的概念，以系统地预测基因集，这些基因集的扰动导致任何给定的细胞类型之间的细胞过渡。此外，据我们所知，这是第一种在不事先知道潜在候选基因和涉及的途径的情况下系统地进行这些预测的方法，为那些知之甚少的系统提供指导。鉴于细胞重编程在医学和基础研究中的兴趣日益浓厚，我们的方法代表了一种有用的计算方法，以帮助该领域的研究人员设计实验策略。干细胞2013；31：2127-2135
Transcription factor cross-repression is an important concept in cellular differentiation. A bistable toggle switch constitutes a molecular mechanism that determines cellular commitment and provides stability to transcriptional programs of binary cell fate choices. Experiments support that perturbations of these toggle switches can interconvert these binary cell fate choices, suggesting potential reprogramming strategies. However, more complex types of cellular transitions could involve perturbations of combinations of different types of multistable motifs. Here, we introduce a method that generalizes the concept of transcription factor cross-repression to systematically predict sets of genes, whose perturbations induce cellular transitions between any given pair of cell types. Furthermore, to our knowledge, this is the first method that systematically makes these predictions without prior knowledge of potential candidate genes and pathways involved, providing guidance on systems where little is known. Given the increasing interest of cellular reprogramming in medicine and basic research, our method represents a useful computational methodology to assist researchers in the field in designing experimental strategies. Stem Cells 2013;31:2127-2135