Renewal through reprogramming

Ring chromosomes are structural aberrations that are often associated with birth defects, mental disabilities and growth retardation. Shinya Yamanaka and colleagues derived human induced pluripotent stem (iPS) cells from patient fibroblasts containing ring chromosomes with large deletions, and found that reprogrammed cells lose the abnormal chromosome and duplicate the wild-type homologue through the compensatory uniparental disomy mechanism. Thus, iPS cells have an intrinsic capacity to purge very damaged chromosomes that have ring structures and deletions spanning hundreds of megabases of DNA. The authors propose that cellular reprogramming might serve a very different function to the familiar one, acting as a means of ‘chromosome therapy’ that reverses combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures.