Imperial College London
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ProfessorTristanRodriguez

Faculty of Medicine, National Heart & Lung Institute

Professor of Cell and Developmental Biology
 
 
 
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Contact

 

+44 (0)20 7594 5448tristan.rodriguez Website

 
 
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Location

 

331ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Price:2021:10.1016/j.devcel.2021.07.019,
author = {Price, CJ and Stavish, D and Gokhale, PJ and Stevenson, BA and Sargeant, S and Lacey, J and Rodriguez, TA and Barbaric, I},
doi = {10.1016/j.devcel.2021.07.019},
journal = {Developmental Cell},
pages = {2455--2470.e10},
title = {Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition},
url = {http://dx.doi.org/10.1016/j.devcel.2021.07.019},
volume = {56},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The appearance of genetic changes in human pluripotent stem cells (hPSCs) presents a concern for their use in research and regenerative medicine. Variant hPSCs that harbor recurrent culture-acquired aneuploidies display growth advantages over wild-type diploid cells, but the mechanisms that yield a drift from predominantly wild-type to variant cell populations remain poorly understood. Here, we show that the dominance of variant clones in mosaic cultures is enhanced through competitive interactions that result in the elimination of wild-type cells. This elimination occurs through corralling and mechanical compression by faster-growing variants, causing a redistribution of F-actin and sequestration of yes-associated protein (YAP) in the cytoplasm that induces apoptosis in wild-type cells. YAP overexpression or promotion of YAP nuclear localization in wild-type cells alleviates their "loser" phenotype. Our results demonstrate that hPSC fate is coupled to mechanical cues imposed by neighboring cells and reveal that hijacking this mechanism allows variants to achieve clonal dominance in cultures.
AU  - Price,CJ
AU  - Stavish,D
AU  - Gokhale,PJ
AU  - Stevenson,BA
AU  - Sargeant,S
AU  - Lacey,J
AU  - Rodriguez,TA
AU  - Barbaric,I
DO  - 10.1016/j.devcel.2021.07.019
EP  - 2470
PY  - 2021///
SN  - 1534-5807
SP  - 2455
TI  - Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition
T2  - Developmental Cell
UR  - http://dx.doi.org/10.1016/j.devcel.2021.07.019
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34407428
UR  - https://www.sciencedirect.com/science/article/pii/S153458072100602X?via%3Dihub
UR  - http://hdl.handle.net/10044/1/91295
VL  - 56
ER  -
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