A new paper is out from a team at The Salk lead by Joseph Ecker that the methylomes of many different human iPS cells. Their conclusion is that while iPS cells and ES cells are generally very similar in terms of the global portions of the genomes that are methylated, iPS cells exhibited hundreds of distinct differences in methylation from ES cells, some of these domains were enormous as well.
So the story continues to build of the ever-growing number of ways in which iPS cells are distinct from ES cells.
Interestingly, of the methylation differences, some were “memories” of the somatic cells from which the iPS cells had been made, but some were unique to the iPS cells. This suggests that some of the methylation changes that occur with cellular reprogramming are stochastic (random).
The differences in methylation between iPS cells and ES cells were most pronounced in centromeric and telomeric regions.
The differences in methylation also correlated with some differences in gene expression as well, indicating that these so-called aberrant methylation events in iPS cells are functionally important. At this point, the big question is what is the functional meaning?
So what does this all mean? The bottom line is that iPS cells and ES cells are similar cell types that nonetheless contain many likely important differences. Thus, iPS cells are not going to be a replacement for ES cells, but rather an additional distinct tool in the regenerative medicine field. I would predict that iPS cells will not be as good as ES cells for some applications, while for other applications iPS cells may very well be better. It is also almost certain that iPS cells are more tumorigenic than ES cells and some of that may be explained by these abnormal methylation patterns.