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理解细胞命运分支点的基因电路,以实现理性的细胞重编程。

Understanding gene circuits at cell-fate branch points for rational cell reprogramming.

机构信息

Institute for Biocomplexity and Informatics, Biological Sciences Bldg, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada, T2N 1N4.

出版信息

Trends Genet. 2011 Feb;27(2):55-62. doi: 10.1016/j.tig.2010.11.002. Epub 2010 Dec 14.

Abstract

Cell-type reprogramming, the artificial induction of a switch of cell lineage and developmental stage, holds great promise for regenerative medicine. However, how does the metazoan body itself 'program' the various cell lineages in the first place? Knowledge of how multipotent cells make cell-fate decisions and commit to a particular lineage is crucial for a rational reprogramming strategy and to avoid trial-and-error approaches in choosing the appropriate set of transcription factors to use. In the past few years, a general principle has emerged in which small gene circuits of cross-inhibition and self-activation govern the decision at branch points of cell development. A formal theoretical treatment of such circuits that deal with their dynamics on the 'epigenetic landscape' could offer some guidance to find the optimal way of cell reprogramming.

摘要

细胞类型重编程,即人工诱导细胞谱系和发育阶段的转换,为再生医学带来了巨大的希望。然而,动物机体本身最初是如何“编程”各种细胞谱系的呢?了解多能细胞如何做出细胞命运决定并确定特定谱系对于合理的重编程策略至关重要,并且可以避免在选择适当的转录因子集合时进行反复试验的方法。在过去的几年中,出现了一个普遍的原则,即交叉抑制和自我激活的小基因电路控制着细胞发育分支点处的决策。对这些电路的动力学进行形式理论处理,可以为寻找细胞重编程的最佳方法提供一些指导。

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