Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells
Summary: Human pluripotent stem cells (hPSCs) acquire genetic changes during their propagation in culture that can affect their use in research and future therapies. To identify the key genes involved in selective advantage during culture adaptation and tumorigenicity of hPSCs, we generated a genome...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900421830261X |
| _version_ | 1811202090072014848 |
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| author | Uri Weissbein Mordecai Peretz Omer Plotnik Ofra Yanuka Ido Sagi Tamar Golan-Lev Nissim Benvenisty |
| author_facet | Uri Weissbein Mordecai Peretz Omer Plotnik Ofra Yanuka Ido Sagi Tamar Golan-Lev Nissim Benvenisty |
| author_sort | Uri Weissbein |
| collection | DOAJ |
| description | Summary: Human pluripotent stem cells (hPSCs) acquire genetic changes during their propagation in culture that can affect their use in research and future therapies. To identify the key genes involved in selective advantage during culture adaptation and tumorigenicity of hPSCs, we generated a genome-wide screening system for genes and pathways that provide a growth advantage either in vitro or in vivo. We found that hyperactivation of the RAS pathway confers resistance to selection with the hPSC-specific drug PluriSIn-1. We also identified that inactivation of the RHO-ROCK pathway gives growth advantage during culture adaptation. Last, we demonstrated the importance of the PI3K-AKT and HIPPO pathways for the teratoma formation process. Our screen revealed key genes and pathways relevant to the tumorigenicity and survival of hPSCs and should thus assist in understanding and confronting their tumorigenic potential. : Cell Biology; Stem Cells Research; Omics; Genomics Subject Areas: Cell Biology, Stem Cells Research, Omics, Genomics |
| first_indexed | 2024-04-12T02:33:15Z |
| format | Article |
| id | doaj.art-8c31be471d0a43c081a78132ad044911 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T02:33:15Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8c31be471d0a43c081a78132ad0449112022-12-22T03:51:40ZengElsevieriScience2589-00422019-01-0111398408Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem CellsUri Weissbein0Mordecai Peretz1Omer Plotnik2Ofra Yanuka3Ido Sagi4Tamar Golan-Lev5Nissim Benvenisty6The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, IsraelThe Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, IsraelThe Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, IsraelThe Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, IsraelThe Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, IsraelThe Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, IsraelThe Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel; Corresponding authorSummary: Human pluripotent stem cells (hPSCs) acquire genetic changes during their propagation in culture that can affect their use in research and future therapies. To identify the key genes involved in selective advantage during culture adaptation and tumorigenicity of hPSCs, we generated a genome-wide screening system for genes and pathways that provide a growth advantage either in vitro or in vivo. We found that hyperactivation of the RAS pathway confers resistance to selection with the hPSC-specific drug PluriSIn-1. We also identified that inactivation of the RHO-ROCK pathway gives growth advantage during culture adaptation. Last, we demonstrated the importance of the PI3K-AKT and HIPPO pathways for the teratoma formation process. Our screen revealed key genes and pathways relevant to the tumorigenicity and survival of hPSCs and should thus assist in understanding and confronting their tumorigenic potential. : Cell Biology; Stem Cells Research; Omics; Genomics Subject Areas: Cell Biology, Stem Cells Research, Omics, Genomicshttp://www.sciencedirect.com/science/article/pii/S258900421830261X |
| spellingShingle | Uri Weissbein Mordecai Peretz Omer Plotnik Ofra Yanuka Ido Sagi Tamar Golan-Lev Nissim Benvenisty Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells iScience |
| title | Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells |
| title_full | Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells |
| title_fullStr | Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells |
| title_full_unstemmed | Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells |
| title_short | Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells |
| title_sort | genome wide screen for culture adaptation and tumorigenicity related genes in human pluripotent stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S258900421830261X |
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