Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells

Uri Weissbein, Mordecai Peretz, Omer Plotnik, Ofra Yanuka, Ido Sagi, Tamar Golan-Lev, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)398-408
Number of pages11
JournaliScience
Volume11
DOIs
StatePublished - 25 Jan 2019

Bibliographical note

Publisher Copyright:
© 2018 The Author(s)

Keywords

  • Cell Biology
  • Genomics
  • Omics
  • Stem Cells Research

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