Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair

Science. 2021 Feb 26;371(6532):eabc4346. doi: 10.1126/science.abc4346.


Organ homeostasis is orchestrated by time- and spatially restricted cell proliferation. Studies identifying cells with superior proliferative capacities often rely on the lineage tracing of a subset of cell populations, which introduces a potential selective bias. In this work, we developed a genetic system [proliferation tracer (ProTracer)] by incorporating dual recombinases to seamlessly record the proliferation events of entire cell populations over time in multiple organs. In the mouse liver, ProTracer revealed more hepatocyte proliferation in distinct zones during liver homeostasis, injury repair, and regrowth. Clonal analysis showed that most of the hepatocytes labeled by ProTracer had undergone cell division. By genetically recording proliferation events of entire cell populations, ProTracer enables the unbiased detection of specific cellular compartments with enhanced regenerative capacities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Cyclin A2 / genetics
  • Hepatectomy
  • Hepatocytes / physiology*
  • Homeostasis
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / genetics
  • Liver / cytology
  • Liver / physiology*
  • Liver Regeneration*
  • Mice


  • CCNA2 protein, mouse
  • Cyclin A2
  • Ki-67 Antigen