Long Interspersed Element 1 (LINE-1 or L1) is an autonomously mobile DNA element found throughout mammalian genomes. L1s have the capability to retrotranspose, or “jump” into other regions of our genome, which can potentially result in cellular dysfunction and genetic disease. Importantly, as “selfish” elements, L1s create heritable insertions— new copies in cells that can be passed down to the next generation. Retrotransposition events in the germline have been detected in transgenic L1 reporter animals and in the early embryo, and exacerbated expression of mobile DNA in the germline has shown to cause sterility in mice. In humans, only two cases of heritable L1 retrotransposition events have been fully explicated; one potentially occurred during female germ cell development, and the other during pluripotent embryonic cell development. However, the exact developmental timing of L1 retrotransposition during this developmental period and the defence mechanisms involved to impede retrotransposition remains unelucidated.
Previously, Richardson et al. 2017 uncovered evidence that L1 may retrotranspose in early mouse primordial germ cells (PGCs). PGCs are specified early during mammalian embryonic development, ultimately giving rise to all germ cells of an adult organism. Little is known about the dynamics of L1 activity and regulation during PGC specification, and the founding population of ~40 mouse PGCs in vivo is technically challenging to study. Hence, we are using an in vitro model to investigate regulation of L1 expression and retrotransposition during cell fate transitions from mESCs to epiblast-like cells (EpiLCs) to primordial germ cell-like cells (PGCLCs). Our work will shed light on the unexplored conflict between L1 activity and genomic defences in this critical developmental niche, as well as further understand L1 mutagenesis as a potential contributor to reproductive dysfunction.