Method of the Year 2010 – direct transdifferentiation induced by defined factors

by Alexey Bersenev on January 17, 2011 · 1 comment

in direct reprogramming, embryonic/iPS, methods

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I was thinking why don’t we highlight the most remarkable method in stem cell research every year? In 2009 it was human iPS cells generation. I think, many of you would agree that in 2010 the most notable method was induced direct transdifferentiation.

Direct transdifferentiation between lineages within one tissue, such as hematopoietic or pancreatic, induced by transcription factors, was shown before. But now we can go beyond of one tissue. Induced direct transdifferentiation is a conversion of one mature cell type to another across the lineages between different tissues or across germ layers, artificially induced in vitro by defined genetic factors. This kind of transdifferentiation called “direct”, because it bypasses the step of full reprogramming to ES cell-like (or iPS cell-like) state.

There were 3 studies, exploring this approach and published in 2010:
1. conversion of mouse skin fibroblasts into functional neurons by Marius Wernig’s lab.
2. conversion of fibroblasts into functional cardiomyocytes by Deepak Srivastava’s lab.
3. conversion of human fibroblasts to blood progenitors by Mickey Bhatia’s lab.

Here is the video about last discovery from Mickey Bhatia’s lab:

What would we expect from this method in 2011? Paul Knoepfler predicts that direct transdifferentiation will compete with iPS cells in terms of safety and translational promise. It’s reminiscent of Thomas Graf’s predictions about great future of this method made in 2008. I’d add that in this or next year (1) we should see the reproducibility of method; (2) we will see more studies on human cells; (3) more “magical conversions” between tissues and (4) will go beyond fibroblasts. Stay tuned!

{ 1 comment… read it below or add one }

Jian-Xin Gao January 20, 2011 at 10:43 am

One of the important issues to verify that fibroblasts could transdifferentiate into diverse tissue type cells is whether these cells are real fibroblasts. In fact, these authors could not exclude the possibility that the prepared fibroblasts might be contaminated by mesenchymal stem cells, which have the potential to differentiate into various types of tissue cells. Theoretically the transdifferentiation efficiency should be much higher than they have observed if real fibroblasts were converted.


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