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LINE-1 retrotransposition in stem cells

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Long INterspersed Element class 1 (LINE-1 or L1) retrotransposons comprise a fifth of the human genome and their ongoing activity continues to impact the genome. Heritable LINE -1 retrotransposition events must occur in cell types that ensure their transmission to newborns. Previous reports have detected LINE -1 expression and activity of engineered elements in cultured human cells that mimic an early embryo. These include human embryonic stem cells (hESCs), human embryonic carcinoma cells (hECs) and induced pluripotent stem cells (iPSCs). Additionally, recent reports have revealed the expression and mobilization of LINE -1 elements in selected somatic human cells including Neuronal Progenitor Cells (NPCs). Here, we used a panel of pluripotent and differentiated cell cultures to inspect the expression and retrotransposition levels of engineered LINE -1 retrotransposons. Remarkably, we observed that LINE -1s are expressed in pluripotent neuronal and embryonic cell types, although expression is higher in embryonic cell types. Additionally, we recapitulated engineered LINE -1 retrotransposition in pluripotent neuronal and embryonic cell types, but observed that retrotransposition rates can vary more than 200-fold among different pluripotent cell types. Indeed, under our experimental conditions, the highest rate of engineered LINE -1 retrotransposition is observed in neuronal cell types. These data suggest that the main load of LINE -1 retrotransposition in humans may occur in selected somatic cells and that most mobilization events will not be transmitted to newborns.

This talk is part of the Departmental Seminar Programme, Department of Veterinary Medicine series.

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