Forcing cells to change lineages


The ability to produce stem cells by induced pluripotency (iPS reprogramming) has rekindled an interest in earlier studies showing that transcription factors can directly convert specialized cells from one lineage to another. Lineage reprogramming has become a powerful tool to study cell fate choice during differentiation, akin to inducing mutations for the discovery of gene functions. The lessons learnt provide a rubric for how cells may be manipulated for therapeutic purposes.

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Figure 1: Examples of transcription factor overexpression or ablation experiments that result in cell fate changes.
Figure 2: Conversion of endothelial cells into haematopoietic cells.
Figure 3: Transcription factor cross-antagonism: the PU.1:GATA1 paradigm.
Figure 4: Timing of transcription factor expression and lineage outcome.
Figure 5: Transcription factor cross-antagonisms in a cascading landscape of unstable and stable cell states.


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We would like to thank J. Sharpe, C. Peterson, J. Brickman and D. Thieffry for feedback and suggestions. T.G. is an ICREA professor and T.E. is supported by an LRF specialist programme.

Author Contributions T.G. and T.E. together conceived the ideas encapsulated in the article and also drafted it jointly. Most of the figures were conceived by T.G. and modified by T.E.

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Correspondence to Thomas Graf.

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Graf, T., Enver, T. Forcing cells to change lineages . Nature 462, 587–594 (2009).

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