ProTracer—a New Genetic System to Seamlessly Record Cell Proliferation in Vivo

Organ homeostasis is orchestrated by timed and spatially restricted cell proliferation. Studies identifying cells with superior proliferative capacity mostly rely on lineage tracing of a subset of cell populations, introducing a potential selective bias. Here, this group developed a genetic system (proliferation tracer, ProTracer) by incorporating dual recombinases to seamlessly record proliferation events of entire cell populations over time in multiple organs. In the liver, ProTracer revealed that a subpopulation of midzonal hepatocytes have superior proliferative capacity during homeostasis, injury repair, and regeneration. Clonal analysis showed that the majority of hepatocytes labeled by ProTracer have undergone cell division. By genetically recording proliferation events of entire cell populations, ProTracer enables unbiased detection of unique cellular compartments with enhanced regenerative capacity.