scholarly journals Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition

2021 ◽  
Author(s):  
Christopher J. Price ◽  
Dylan Stavish ◽  
Paul J. Gokhale ◽  
Ben A. Stevenson ◽  
Samantha Sargeant ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Wild Type ◽  
Cell Competition

scholarly journals Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition

2019 ◽  
Author(s):  
Christopher J. Price ◽  
Dylan Stavish ◽  
Paul J. Gokhale ◽  
Samantha Sargeant ◽  
Joanne Lacey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Competitive Interactions ◽  
Mechanical Compression ◽  
Wild Type ◽  
Cell Competition ◽  
Genetic Changes ◽  
Variant Cell ◽  
Diploid Cells

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.

scholarly journals Genetically Variant Human Pluripotent Stem Cells Selectively Eliminate Wild-Type Counterparts Through YAP-Mediated Cell Competition

2019 ◽  
Author(s):  
Christopher J. Price ◽  
Dylan Stavish ◽  
Paul J. Gokhale ◽  
Samantha Sargeant ◽  
Joanne Lacey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Wild Type ◽  
Cell Competition

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 ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Cell Competition

Differentiation of human pluripotent stem cells into airway epithelial cells

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Ulrich ◽  
S Weinreich ◽  
R Haller ◽  
S Menke ◽  
R Olmer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Pluripotent Stem Cells ◽  
Airway Epithelial Cells ◽  
Human Pluripotent Stem Cells ◽  
Airway Epithelial

326-LB: BCL-xL/BCL2L1 Is a Critical Anti-Apoptotic Protein that Suppresses BAK to Promote Pancreatic Specification from Human Pluripotent Stem Cells

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 ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Apoptotic Protein
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