Final Report Summary - SOMATIC_MOSAICISM (LINE-1 retrotransposition in human somatic cells)
Once we have obtained and characterized these cell lines, we will differentiate them in vitro and in vivo (in mice) into the three germ layers. Switching on retrotransposition will allow us to determine its relative rate depending on the germ layer. We have furthermore characterized the endogenous expression of LINEs on the RNA and protein level in the different germ layers, with the result that NPCs moderately express LINE-1 RNA and protein, while the other germ layers show much lower levels. This could explain the potential of NPCs to sustain high levels of somatic retrotransposition.
Finally, we have been able to successfully map several new LINE-1 insertions in hESCs with a new mapping protocol. This will allow us to detect hot spots of insertion depending on each germ layer.
In parallel, using other funds of the host lab and with the help of a talented PhD student, we have been developing a similar approach using an inducible LINE element in zebrafish (see attached report on the zebrafish project). The comparison of both model organisms will allow us to draw conclusions on whether somatic LINE activity is evolutionary conserved and what is its impact in vertebrates.