英国剑桥大学Ludovic Vallier、Daniel Ortmann等研究人员发现，遗传变异可影响初始多能干细胞的表型变异。2020年8月13日，《细胞—干细胞》在线发表了这一成果。

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

Author: 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

Issue&Volume: 2020-08-13

Abstract: 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 and genetic factors that influence stem cell behavior. Naive culture conditions minimize epigenetic fluctuation, potentially overcoming differences in PSC line differentiation potential. Here we derived PSCs from distinct mouse strains under naive conditions and show that lines from distinct genetic backgrounds have divergent differentiation capacity, confirming a major role for genetics in PSC phenotypic variability. This is explained in part through inconsistent activity of extra-cellular signaling, including the Wnt pathway, which is modulated by specific genetic variants. Overall, this study shows that genetic background plays a dominant role in driving phenotypic variability of PSCs.

DOI: 10.1016/j.stem.2020.07.019

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30357-X