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  • Variability in the Generation of Induced Pluripotent Stem Cells: Importance for Disease Modeling

    Author(s)
    Vitale, Alejandra M
    Matigian, Nicholas A
    Ravishankar, Sugandha
    Bellette, Bernadette
    Wood, Stephen A
    Wolvetang, Ernst J
    Mackay-Sim, Alan
    Griffith University Author(s)
    Mackay-Sim, Alan
    Matigian, Nicholas
    Bellette, Bernadette
    Ravishankar, Sugandha
    Wood, Stephen A.
    Vitale, Alejandra M.
    Year published
    2012
    Metadata
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    Abstract
    In the field of disease modeling, induced pluripotent stem cells (iPSCs) have become an appealing choice, especially for diseases that do not have an animal model. They can be generated from patients with known clinical features and compared with cells from healthy controls to identify the biological bases of disease. This study was undertaken to determine the variability in iPSC lines derived from different individuals, with the aim of determining criteria for selecting iPSC lines for disease models. We generated and characterized 18 iPSC lines from eight donors and considered variability at three levels: (a) variability ...
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    In the field of disease modeling, induced pluripotent stem cells (iPSCs) have become an appealing choice, especially for diseases that do not have an animal model. They can be generated from patients with known clinical features and compared with cells from healthy controls to identify the biological bases of disease. This study was undertaken to determine the variability in iPSC lines derived from different individuals, with the aim of determining criteria for selecting iPSC lines for disease models. We generated and characterized 18 iPSC lines from eight donors and considered variability at three levels: (a) variability in the criteria that define iPSC lines as pluripotent cells, (b) variability in cell lines from different donors, and (c) variability in cell lines from the same donor. We found that variability in transgene expression and pluripotency marker levels did not prevent iPSCs from fulfilling all other criteria for pluripotency, including teratoma formation. We found low interindividual and interclonal variability in iPSCs that fulfilled the most stringent criteria for pluripotency, with very high correlation in their gene expression profiles. Interestingly, some cell lines exhibited reprogramming instability, spontaneously regressing from a fully to a partially reprogrammed state. This was associated with a low percentage of cells expressing the pluripotency marker stage-specific embryonic antigen-4. Our study shows that it is possible to define a similar "ground state" for each cell line as the basis for making patient versus control comparisons, an essential step in order to identify disease-associated variability above individual and cell line variability.
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    Journal Title
    Stem Cells Translational Medicine
    Volume
    1
    DOI
    https://doi.org/10.5966/sctm.2012-0043
    Copyright Statement
    Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
    Subject
    Regenerative Medicine (incl. Stem Cells and Tissue Engineering)
    Neurosciences not elsewhere classified
    Biochemistry and Cell Biology
    Medical Biotechnology
    Clinical Sciences
    Publication URI
    http://hdl.handle.net/10072/48641
    Collection
    • Journal articles

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