Anthony L. Komaroff, MD

Depleting a single molecule from a differentiated cell allows almost complete transformation to the embryonic state.

Introducing only four genes into fully differentiated skin cells can transform them into embryonic-like stem cells (induced pluripotent stem [iPS] cells), similar to those that exist transiently shortly after conception. In other words, we can turn back the clock, and we can create for individuals their own genetically identical embryonic stem cells. Such cells could be transformed into replacements for cells killed by disease — cardiomyocytes or neurons, for example. Disease in animals has been treated successfully in this way (NEJM JW Gen Med Dec 29 2008). This landmark discovery was honored with the Nobel Prize in 2012.

Practical obstacles abound, however, in applying this breakthrough in stem cell biology to treating human disease. One huge obstacle has been the inefficiency of creating iPS cells: Only about 1% of differentiated cells into which the genes are introduced are converted into iPS cells. A team from Israel now reports that depleting a single molecule (called Mbd3) allows nearly 100% of cells to be transformed into iPS cells. Their work also delineates the mechanism for this effect.

Citation(s):

Rais Y et al. Deterministic direct reprogramming of somatic cells to pluripotency. Nature 2013 Oct 3; 502:65.

Loh KM and Lim B.Stem cells: Close encounters with full potential. Nature 2013 Oct 3; 502:41.