Barcoding the mouse germline to the next generation

Germline is the only cell lineage transmitted to the next generation. De novo mutations occurring in these cells will be conveyed by sperm and eggs to the next generation. Therefore, the fate behaviours of a germ cell clone are critical for transmitting the mutations in their genome. However, the germline cells’ clonal dynamics remains largely unknown in mammals.

Using a DNA barcoding methodology, we are analysing the clonal lineage behaviour of the entire germ cell population in male mice – from immediately after specification in early embryos through primordial germ cell proliferation, sex determination, sperm stem cell establishment and maintenance, and spermatogenesis. We further analysed the transmission of barcoded genomes to the next generation. We found that a considerable fraction of clones get extinct during early development. While, germ cells surviving this stage maintain their clonal diversity till adulthood, proportionally transmitted to the next generations. I would discuss the potential significance and regulatory mechanisms of observed clonal dynamics.