Human pluripotent stem cells have an unlimited capacity to self-renew in culture. This feature, along with their ability to become any cell type in the adult body, makes them a unique tool to study human biology in health and disease. Unfortunately, human pluripotent stem cells have a propensity to acquire genetic abnormalities in culture that may limit their scientific and clinical use. Among the most prevalent genomic changes found in pluripotent stem cells are various forms of over-representation of sequences on the long arm of chromosome 20, with up to 20% of tested cultures containing such an aberration. One such anomaly, the isochromosome 20 mutation, is also found in amniocentesis analyses.  In  this episode, Martin Pera is joined by three scientists, who along with their colleagues, authored the recent paper published in Stem Cell Reports entitled, The isochromosome 20q abnormality of pluripotent cells interrupts germ layers differentiation.  This publication explores the effects of this particular anomaly on the ability of pluripotent stem cells to differentiate both spontaneously and by directed differentiation.  The results were surprising, with implications for understanding early development and the potential therapeutic use of pluripotent stem cells. The authors  also discuss some of the challenges of working with pluripotent stem cells. Guests Ivana Barbaric, PhD, University of Sheffield, UK Pete Coffey, PhD, University College London and the University of California, Santa Barbara, US Loriana Vitillo, PhD, University College London, UK Host Martin Pera, PhD, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory Twitter: @martinperaJAX Supporting Content The isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation, Vitillo, et. al., Stem Cell Reports (2023) About Stem Cell Reports Stem Cell Reports is the open access journal of the ISSCR for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Twitter: @StemCellReports About ISSCR With more than 4,600 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Jack Mosher, Scientific Advisor Voice Work Ben Snitkoff