Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells
نویسندگان
چکیده
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.
منابع مشابه
Deep Sequencing Reveals Low Incidence of Endogenous LINE-1 Retrotransposition in Human Induced Pluripotent Stem Cells
Long interspersed element-1 (LINE-1 or L1) retrotransposition induces insertional mutations that can result in diseases. It was recently shown that the copy number of L1 and other retroelements is stable in induced pluripotent stem cells (iPSCs). However, by using an engineered reporter construct over-expressing L1, another study suggests that reprogramming activates L1 mobility in iPSCs. Given...
متن کاملReprogramming somatic cells into iPS cells activates LINE-1 retroelement mobility.
Long interspersed element-1 (LINE-1 or L1) retrotransposons account for nearly 17% of human genomic DNA and represent a major evolutionary force that has reshaped the structure and function of the human genome. However, questions remain concerning both the frequency and the developmental timing of L1 retrotransposition in vivo and whether the mobility of these retroelements commonly results in ...
متن کاملInduced pluripotent stem cells (iPSCs) based approaches for hematopoietic cancer therapy
Induced pluripotent stem cells (iPSCs) are reprogrammed from somatic cells through numerous transcription factors. Human induced pluripotent stem cell approaches are developing as a hopeful strategy to improve our knowledge of genetic association studies and the underlying molecular mechanisms. Rapid progression in stem cell therapy and cell reprogramming provides compelling reasons for its fe...
متن کاملEstablishment and the importance of chicken pluripotent stem cells and their role in vaccine production: review article
Chick embryos are a great historical research model in basic and applied sciences. Along with other animal models, avian and specifically chicken embryo has been attended, as well. Avian fertilized eggs as a natural bioreactor are an efficient tool for producing recombinant proteins and vaccines manufacturing. Due to the limitations of birds' eggs for viral replication, avian stem cells culture...
متن کاملI-54: New Models for Human and Mouse Genetic
The possibility to reprogram somatic human cells will greatly and deeply change genetic approach and allow the development of new tools to study genetics diseases. Indeed, our ability to study human genetic diseases suffers from the lack of valid in vitro models. The latter should (i) be originating from human primary cells, (ii) be able to self-renew for a long time and (iii) be able to differ...
متن کامل