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Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations

Author

Listed:
  • Florian T. Merkle

    (Harvard University
    Harvard University
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Stem Cell Institute)

  • Sulagna Ghosh

    (Harvard University
    Harvard University
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Stem Cell Institute)

  • Nolan Kamitaki

    (Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Jana Mitchell

    (Harvard University
    Harvard University
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Stem Cell Institute)

  • Yishai Avior

    (The Azrieli Center for Stem Cells and Genetic Research, Institute of Life Sciences, Hebrew University of Jerusalem)

  • Curtis Mello

    (Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Seva Kashin

    (Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Shila Mekhoubad

    (Harvard University
    Harvard University
    Harvard Stem Cell Institute
    Biogen)

  • Dusko Ilic

    (Stem Cell Laboratories, Guy’s Assisted Conception Unit, Faculty of Life Sciences and Medicine, King’s College London)

  • Maura Charlton

    (Harvard University
    Harvard University
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Stem Cell Institute)

  • Genevieve Saphier

    (Harvard University
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Stem Cell Institute)

  • Robert E. Handsaker

    (Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Giulio Genovese

    (Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Shiran Bar

    (The Azrieli Center for Stem Cells and Genetic Research, Institute of Life Sciences, Hebrew University of Jerusalem)

  • Nissim Benvenisty

    (The Azrieli Center for Stem Cells and Genetic Research, Institute of Life Sciences, Hebrew University of Jerusalem)

  • Steven A. McCarroll

    (Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Kevin Eggan

    (Harvard University
    Harvard University
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
    Harvard Stem Cell Institute)

Abstract

The authors surveyed whole-exome and RNA-sequencing data from 252 unique pluripotent stem cell lines, some of which are in the pipeline for clinical use, and found that approximately 5% of cell lines had acquired mutations in the TP53 gene that allow mutant cells to rapidly outcompete non-mutant cells, but do not prevent differentiation.

Suggested Citation

  • Florian T. Merkle & Sulagna Ghosh & Nolan Kamitaki & Jana Mitchell & Yishai Avior & Curtis Mello & Seva Kashin & Shila Mekhoubad & Dusko Ilic & Maura Charlton & Genevieve Saphier & Robert E. Handsaker, 2017. "Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations," Nature, Nature, vol. 545(7653), pages 229-233, May.
    • Handle: RePEc:nat:nature:v:545:y:2017:i:7653:d:10.1038_nature22312
    DOI: 10.1038/nature22312
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    Cited by:

    1. Congyi Lu & Görkem Garipler & Chao Dai & Timothy Roush & Jose Salome-Correa & Alex Martin & Noa Liscovitch-Brauer & Esteban O. Mazzoni & Neville E. Sanjana, 2023. "Essential transcription factors for induced neuron differentiation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Arianna Moiani & Gil Letort & Sabrina Lizot & Anne Chalumeau & Chloe Foray & Tristan Felix & Diane Clerre & Sonal Temburni-Blake & Patrick Hong & Sophie Leduc & Noemie Pinard & Alan Marechal & Eduardo, 2024. "Non-viral DNA delivery and TALEN editing correct the sickle cell mutation in hematopoietic stem cells," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Sulagna Ghosh & Ralda Nehme & Lindy E. Barrett, 2022. "Greater genetic diversity is needed in human pluripotent stem cell models," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    4. Ju-Chan Park & Yun-Jeong Kim & Gue-Ho Hwang & Chan Young Kang & Sangsu Bae & Hyuk-Jin Cha, 2024. "Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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