Researchers have recently determined the source of genetic mutations found in induced pluripotent stem (iPS) cells. In recent years, scientists have developed ways of reprogramming cells, such as those derived from blood or skin, to revert back to an embryonic stem cell-like state. These stem cells have the potential to give rise not only to new cells of the original type but also to more stem cells and to cells of many different types of tissues. One technique involves the introduction of three to four genes into adult cells that direct the reprogramming of these cells into iPS cells. Recent studies assessing the genetic integrity of iPS cells have found mutations that could limit the therapeutic potential of these cells, but the origins of these mutations have not been clear.
Scientists determined the complete sequence of all the DNA—the “genome”—from 10 different mouse iPS cell lines derived from three different original, or parental, cells. The entire genomes were sequenced to determine the number and location of any mutations. Hundreds of mutations were detected in each iPS cell line genome. By comparing the genome sequences of the parental cells to those of derivative iPS cells, the researchers concluded that most of the genetic mutations in iPS cell lines were not caused during the reprogramming process but rather were derived from mutations that pre-existed in the parental cells.
This study illustrates the importance of selecting the most appropriate adult cell to undergo the reprogramming process to form iPS cells, because any mutations that exist in the parental cell will be passed on to the iPS cells. Knowledge gained from sequencing iPS cell genomes may help to improve the selection and derivation of iPS cells such that these cells can be more safely used for regenerative therapies.
Young MA, Larson DE, Sun C-W, et al. Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell 10: 570-582, 2012.