Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation

• DOI: 10.1016/j.stem.2020.07.019
• Publication Date: 2020-08-13T14:54:33Z
• Authors: Daniel Ortmann; Stephanie Brown; Anne Czechanski; Selcan Aydin; Daniele Muraro; Yuanhua Huang; Rute A. Tomaz; Anna Osnato; Giovanni Canu; Brandon T. Wesley; Daniel A. Skelly; Oliver Stegle; Ted Choi; Gary A. Churchill; Christopher L. Baker; Peter J. Rugg-Gunn; Steven C. Munger; Laura G. Reinholdt; Ludovic Vallier
• Keywords: Genetic Variability

Variability among pluripotent stem cell (PSC) lines is a prevailing issue that hampers not only experimental reproducibility but also large-scale applications and personalized cell-based therapy. This variability could result from epigenetic genetic factors influence behavior. Naive culture conditions minimize fluctuation, potentially overcoming differences in PSC line differentiation potential. Here we derived PSCs distinct mouse strains under naive show backgrounds have divergent capacity, confirming major role for genetics phenotypic variability. explained part through inconsistent activity of extra-cellular signaling, including the Wnt pathway, which modulated by specific variants. Overall, this study shows background plays dominant driving PSCs.