Document Type
Article
Publication Date
9-3-2020
Keywords
JMG, JAXCC
JAX Source
Cell Stem Cell 2020 Sep 3; 27(3):470-481.e6
Volume
27
Issue
3
First Page
470
Last Page
481
ISSN
1875-9777
PMID
32795399
DOI
https://doi.org/10.1016/j.stem.2020.07.019
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.
Recommended Citation
Ortmann D,
Brown S,
Czechanski A,
Aydin S,
Muraro D,
Huang Y,
Tomaz R,
Osnato A,
Canu G,
Wesley B,
Skelly D,
Stegle O,
Choi T,
Churchill G,
Baker CL,
Rugg-Gunn P,
Munger SC,
Reinholdt L,
Vallier L.
Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation. Cell Stem Cell 2020 Sep 3; 27(3):470-481.e6