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J Cell Sci. 2012 Jun 1;125(Pt 11):2553-60. doi: 10.1242/jcs.084822. Epub 2012 Jun 26.

Cellular reprogramming--lowering gravity on Waddington's epigenetic landscape.

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Center for iPS Cell Research and Application, Kyoto University 53, Sakyo-ku, Kyoto, Japan.


During development, cell fate is specified precisely through programming by multiple complex elements and processes, including chromatin modifications that result in epigenetic marks. Once determined, cell fate is specified further only through maturation processes, which include differentiation and senescence. However, recent studies have shown that it is possible to influence cell fate through artificial manipulation. For example, the exogenous expression of a set of transcription factors can result in the reprogramming of differentiated skin fibroblasts to a pluripotent state. In addition, recent reports have demonstrated the directed reprogramming of one type of differentiated somatic cell to another type of differentiated somatic cell, without rejuvenation to a pluripotent state. Reprogramming factors blur the boundaries between different cell fates, which can never meet, as if the hierarchy were flattened by 'lowering gravity'. Although attempts to use direct reprogramming to generate certain cell types, such as those found in the kidneys and the lungs, have remained unsuccessful, recent advances suggest that we are nearing the identification of determinants that allow cells to be directly reprogrammed into cell types from all organs in the not too distant future. This Commentary summarises our current knowledge on cellular reprogramming, and more specifically, recent advances in direct reprogramming to generate a variety of cell types.

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