MYCN-Driven Cell Competition Provokes Interspecies Chimerism Using Human Pluripotent Stem Cells

2020 ◽  
Author(s):  
Yanling Zhu ◽  
Zhishuai Zhang ◽  
Nana Fan ◽  
Ke Huang ◽  
Jiaming Gu ◽  
...  
Author(s):  
Christopher J. Price ◽  
Dylan Stavish ◽  
Paul J. Gokhale ◽  
Ben A. Stevenson ◽  
Samantha Sargeant ◽  
...  

2019 ◽  
Author(s):  
Christopher J. Price ◽  
Dylan Stavish ◽  
Paul J. Gokhale ◽  
Samantha Sargeant ◽  
Joanne Lacey ◽  
...  

AbstractThe appearance of genetic changes in human pluripotent stem cells (hPSCs) presents a concern for their use in research and regenerative medicine. Variant hPSCs harbouring recurrent culture-acquired aneuploidies display growth advantages over wild-type diploid cells, but the mechanisms yielding 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 resulting in 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 YAP in the cytoplasm that induces apoptosis in wild-type cells. Importantly, YAP overexpression in wild-type cells is sufficient to alleviate their loser phenotype. Our results demonstrate that hPSC fate is coupled to mechanical cues imposed by neighbouring cells and reveal that hijacking this mechanism allows variants to achieve clonal dominance in cultures.


2019 ◽  
Author(s):  
Christopher J. Price ◽  
Dylan Stavish ◽  
Paul J. Gokhale ◽  
Samantha Sargeant ◽  
Joanne Lacey ◽  
...  

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Ulrich ◽  
S Weinreich ◽  
R Haller ◽  
S Menke ◽  
R Olmer ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 326-LB
Author(s):  
LARRY SAI WENG LOO ◽  
ADRIAN TEO ◽  
SOUMITA GHOSH ◽  
ANDREAS ALVIN PURNOMO SOETEDJO ◽  
LINH NGUYEN ◽  
...  

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