Excision of Reprogramming Transgenes Improves the Differentiation Potential of iPS Cells Generated with a Single Excisable Vector

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  • Cesar A. Sommer
    Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • Andreia Gianotti Sommer
    Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • Tyler A. Longmire
    Boston University Pulmonary Center, and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • Constantina Christodoulou
    Boston University Pulmonary Center, and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • Dolly D. Thomas
    Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • Monica Gostissa
    The Howard Hughes Medical Institute, Children's Hospital Boston, and Department of Genetics, Harvard Medical School, Boston, Massachusetts
  • Fred W. Alt
    The Howard Hughes Medical Institute, Children's Hospital Boston, and Department of Genetics, Harvard Medical School, Boston, Massachusetts
  • George J. Murphy
    Section of Hematology and Medical Oncology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • Darrell N. Kotton
    Boston University Pulmonary Center, and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • Gustavo Mostoslavsky
    Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts

書誌事項

公開日
2009-11-10
権利情報
  • https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
DOI
  • 10.1002/stem.255
公開者
Oxford University Press (OUP)

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説明

<jats:title>Abstract</jats:title> <jats:p>The residual presence of integrated transgenes following the derivation of induced pluripotent stem (iPS) cells is highly undesirable. Here we demonstrate efficient derivation of iPS cells free of exogenous reprogramming transgenes using an excisable polycistronic lentiviral vector. A novel version of this vector containing a reporter fluorochrome allows direct visualization of vector excision in living iPS cells in real time. We find that removal of the reprogramming vector markedly improves the developmental potential of iPS cells and significantly augments their capacity to undergo directed differentiation in vitro. We further propose that methods to efficiently excise reprogramming transgenes with minimal culture passaging, such as those demonstrated here, are critical since we find that iPS cells may acquire chromosomal abnormalities, such as trisomy of chromosome 8, similar to embryonic stem cells after expansion in culture. Our findings illustrate an efficient method for the generation of transgene-free iPS cells and emphasize the potential beneficial effects that may result from elimination of integrated reprogramming factors. In addition, our results underscore the consequences of long-term culture that will need to be taken into account for the clinical application of iPS cells.</jats:p>

収録刊行物

  • Stem Cells

    Stem Cells 28 (1), 64-74, 2009-11-10

    Oxford University Press (OUP)

被引用文献 (9)*注記

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