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Archived Comments for: Retrotransposition in tumors and brains

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  1. Lack of proof for ongoing endogenous retrotransposition in induced pluripotent stem cells

    Gerald Schumann, Paul-Ehrlich-Institut

    17 April 2014

    John Goodier stated in his commentary (Mobile DNA 2014, 5:11) that ‘recent investigations have documented ongoing retrotransposition in (….) induced pluripotent stem cells.’ This conclusion is incorrect, because to date no evidence has been published demonstrating ongoing mobilization of endogenous retrotransposons in induced pluripotent stem cells (iPSCs). None of the listed references provides any evidence for this statement. It has been reported that fibroblast-derived human iPSCs support retrotransposition of an engineered, plasmid-based L1 reporter element, and that both L1 full-length transcripts and L1-encoded ORF1 proteins are expressed from endogenous elements (Wissing et al. [2012] Hum. Mol. Genet. 21: 208-218). However, these findings do not constitute any evidence for ongoing retrotransposition of endogenous transposable elements in iPSCs.

    Competing interests

    None
  2. Response and update

    John Goodier, Johns Hopkins University School of Medicine

    27 October 2014

    Dr. Schumann was correct in his comment. Careless phrasing on my part implied that evidence existed for active endogenous retrotransposition in iPS cells when it did not. In fact, the only study available at that time was Wissing et al. (2012), one that tested retrotransposition competency in derived iPS cell lines using engineered L1-reporter constructs only.

    Now, a new publication suggests that endogenous retrotransposition may indeed occur at low levels in iPS cells (Arokium et al. Deep Sequencing Reveals Low Incidence of Endogenous LINE-1 Retrotransposition in Human Induced Pluripotent Stem Cells. PLoS One. 2014 9(10):e108682). These authors begin by demonstrating that their 454 high-throughput sequencing approach, based on L1-Seq, detects 94% of known germline insertions, even for single copy reads. They then describe seven unique single-copy reads from two sequenced iPS cell lines, not present in the parental human fetal fibroblast line, and absent from any database of known polymorphic L1s. This is taken as evidence for de novo retrotransposition specific to the iPS cell lines. Unfortunately, the authors were unable to confirm these insertions by downstream conventional PCR, a failure they attribute to the presence of these putative new L1s in only a small subset of the total population of iPS cells, and therefore below the limit of PCR detection. While this is one reasonable assumption, further investigations are required to confirm with certainty that active endogenous retrotransposition is a feature of iPS cells.

    Competing interests

    None declared

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