Small but Significant: Inter- and Intrapatient Variations in iPS Cell–based Disease Modeling

Last year the Nobel Prize in Physiology or Medicine was awarded to John B. Gurdon and Shinya Yamanaka for their groundbreaking research on reprogramming of somatic cells.[1,2] Using a set of just four transcription factors, Yamanaka demonstrated that somatic cells could be reprogrammed into induced pluripotent stem (iPS) cells that exhibited most, if not all, of the hallmarks of bona fide pluripotent stem cells. This observation immediately raised the prospect of patient-specific pluripotent stem cells both for therapeutic applications using stem cell-based transplants and for disease modeling. However, six years after the appearance of this landmark study, the suitability of patient-specific iPS cells for disease modeling or drug screening remains challenged by the existence of clone-to-clone variability that can complicate such studies.