Cellular identity and transdifferentiation – interview with Thomas Graf

by Alexey Bersenev on February 11, 2011 · 0 comments

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More than a year ago, the greatest online resource – Nature Reports Stem Cells was discontinued. But archive is still available for readers. Interestingly, the page to which i keep returning has become Thomas Graf’s interview.

Thomas Graf – Professor atf the Centre for Genomic Regulation in Barcelona.
The interview was published in October 2008 and many of his predictions became reality in 2010. Some of my favorite excerpts below:

About the first experiments on direct transdifferentiation by defined genetic factors:

In the early 1990s we had developed chicken cell lines that could be switched from an erythroid [red blood] into a myeloid [white blood] fate by activated Ras and we found that GATA-1 became downregulated. We then asked what would happen if we expressed GATA-1 in the myeloid lines, expecting at best the ectopic activation of some haemoglobin production. To our surprise, the cells completely changed phenotype.

About the possibilities and benefits of inter-lineage direct transdifferentiation:

If we can do this directly it would simplify therapeutic protocols tremendously. It is never going to be trivial for a clinic to generate induced pluripotent stem (iPS) cells for a patient and then coax these cells into the cell type they require for cell therapy in large numbers without the danger of producing contaminating cells that might be tumorigenic. If you had a way to do this directly, it would be an enormous advantage.

About the difference between reprogramming and transdifferentiation:

Cell reprogramming involves the generation of ES cells, or cells that closely resemble them. Induced transdifferentiation/lineage conversions, on the other hand, do not seem to go through an iPS cell state, and by that criterion, the two processes are different. However, it is still possible that, at least in some instances, lineage conversions also involve some kind of retrodifferentiation.

Advice do you have for scientists entering this field now:

Do not join the iPS craze unless you are pretty sure that you have a unique angle or question. Directed transdifferentiation could become a hot new area; it is not yet too crowded.

read full interview

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