Pluto Bioinformatics

GSE122215: Peg10 regulation of TSC differentiation

Bulk RNA sequencing

The prevailing dogma that approximately 50% of our genome is junk DNA composed of transposable elements and retroviral insertions has recently been challenged. It has become evident that our genome has taken advantage of these transposable elements and uses them as a source of DNA to generate novel genes, which subsequently allow the organism to evolve. This process is termed domestication of transposable elements and the majority of these genes have been found to be essential for the existence of the organism.; One of these developmentally essential domesticated genes: Peg10 (paternally expressed gene 10), was derived from a Ty3/gyspy LTR retrotransposon, yet lost its ability to transpose due to mutational events during its domestication. Remarkably, Peg10 has successfully maintained its Gag and Pol-like domains for millions of years.; Peg10 orthologues are expressed in eutherian mammals and are essential for placentogenesis. To address the functional mechanisms of Peg10 we studied it in Trophoblast Stem Cells (TSCs). We find that the Gag of Peg10 is fully active: it promotes budding of vesicles, akin to the viral counterpart that catalyzes the budding of viruses. TSCs, deleted for Peg10, fail to differentiate into placental lineages, underscoring a critical role in lineage specification. This paper discusses our efforts to characterize the contents of Peg10 vesicles and whether such vesicles regulate lineage specification. SOURCE: Rohit Reja (rejar@gene.com) - Genentech