IPS Genomes Investigated

Abstract

A series of recent articles have examined the genomes and epigenomes of induced pluripotent stem (iPS) cell lines. The results appear discouraging for the clinical future of iPS cells, but researchers don't seem worried. In August 2006, Kazutoshi Takahashi and Shinya Yamanaka reported that just four specific factors were sufficient to convert a fully differentiated adult cell into a pluripotent stem cell.1 Not only was the concept scientifically gripping, but also the implications for the technique's clinical application were tremendous. A patient's own cells might be used to generate replacement cells for therapy, avoiding the worry of transplant rejection, as well as the ethical concerns and tricky techniques of embryonic stem (ES) cell generation. So began a proliferative burst of related research studies. Publications on iPS cell research have become so plentiful, in fact, that it is hard to believe the field is not yet five years old. New approaches to improve safety and efficiency have been suggested, different adult cell types have been converted, and numerous disease model cell lines have been made, and yet, as the fifth birthday draws near, a series of recent research articles threaten to spoil the party. The reports reveal that the genomes of iPS cell lines exhibit chromosome abnormalities, residual epigenetic marks from the parent somatic cell type, and a higher than normal number of coding sequence mutations. In one recent article, for example, Pasi et al2 report that genomic deletions and amplifications (copy number variations) are abundant at fragile sites in the genomes of mouse iPS cells. In another, Hussein et al3 show that such copy number variation exists in human iPS cell lines too, and that, on average, copy number variation is two-fold higher in iPS cells …