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Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells. | LitMetric

AI Article Synopsis

  • Human induced pluripotent stem cells (hiPSCs) can grow indefinitely and can transform into various cell types, but they may have genetic issues during their creation.
  • Research by Wissing and colleagues discovered that the process of making hiPSCs can cause the movement of certain retrotransposons, which are genetic elements that can copy and insert themselves into genomes.
  • By studying multiple hiPSC and hESC lines, they found that several instances of these genetic insertions occur, some of which disrupt important gene functions, leading to potential consequences for cell behavior.

Article Abstract

Human induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives of the three primary germ layers. Genetic and epigenetic abnormalities have been reported by Wissing and colleagues to occur during hiPSC derivation, including mobilization of engineered LINE-1 (L1) retrotransposons. However, incidence and functional impact of endogenous retrotransposition in hiPSCs are yet to be established. Here we apply retrotransposon capture sequencing to eight hiPSC lines and three human embryonic stem cell (hESC) lines, revealing endogenous L1, Alu and SINE-VNTR-Alu (SVA) mobilization during reprogramming and pluripotent stem cell cultivation. Surprisingly, 4/7 de novo L1 insertions are full length and 6/11 retrotransposition events occurred in protein-coding genes expressed in pluripotent stem cells. We further demonstrate that an intronic L1 insertion in the CADPS2 gene is acquired during hiPSC cultivation and disrupts CADPS2 expression. These experiments elucidate endogenous retrotransposition, and its potential consequences, in hiPSCs and hESCs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729875PMC
http://dx.doi.org/10.1038/ncomms10286DOI Listing

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