Ortmann, D;
Brown, S;
Czechanski, A;
Aydin, S;
Muraro, D;
Huang, Y;
Tomaz, RA;
... Vallier, L; + view all
(2020)
Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation.
Cell Stem Cell
10.1016/j.stem.2020.07.019.
(In press).
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Abstract
Summary: 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.
| Type: | Article |
|---|---|
| Title: | Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.stem.2020.07.019 |
| Publisher version: | https://doi.org/10.1016/j.stem.2020.07.019 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | pluripotent stem cells, mouse embryonic stem cells, differentiation, variability, ground state, naïve, genetics, signaling, eQTL |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10108166 |
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