New stem cell journal from "Cell"

It was bound to happen, cell, the top tier journal when it comes to cell biology spun off a new journal dedicated to stem cells last week. It took a few days for the university to get access, but I was finally able to peruse it today. I had a little bit of a double take actually regarding the landmark paper published in this first edition. You may have heard that Myc, sox2, oct4 and klf4 are sufficient to reprogram fibroblasts into stem cells. In fact you may have heard of it a full year ago, as this experiment was done by a Japanese group (Takahashi K, Yamanaka S.) and published in Cell. This new paper seems to be almost the same experiments except it takes 12 American scientists to do the work of 2 Japanese :). And if that wasn't confusing enough, another team from the Whitehead Institute also published similar findings last week in nature. This latter group is a proponent of the bivalent histone code regulation of key stem-cell factor. The idea is that both repressive and active histone modifications mark the promoters of these factors making them easily inducible but also primed for repression may the cell wish to differentiate. As talked about previously on the bayblab, these bivalent promoters may be suceptible to dysregulation by epigenetic factors (trithorax/polycomb) over time and may be one of the mechanisms to transformation...
While we have talked about sox2, klf4, c-myc and oct4 when the first paper came around there are a few things worth highlighting this time around... While the ectopic expression of these transcription factors is required for the reprogramming it is not really sufficient. There was a large lag period between the expression and the reprogramming, suggesting there is an additional stochastic event that needs to occur. Also, c-myc is the odd one of these transcription factor as it tends to regulate very large areas of chromatin rather than just specific genes. Perhaps the lag is due to chance remodelling event over large areas. For example the authors show that the inactive X chromosome is re-activated by these factors. So this begs the question: what happens to the chromatin, how is the histone code changed, what is the lag for, would expression of members of the trithorax/polycomb make the process more efficient?

More on that later....