Endogenous beta-galactosidase activity marks a TREM2-expressing Kupffer cell population in injured livers of Lgr5-LacZ and wild-type mice

FEBS Lett. 2020 Mar;594(5):958-970. doi: 10.1002/1873-3468.13669. Epub 2019 Nov 28.


Lgr5-LacZ mice harbor the Escherichia coli LacZ gene encoding β-galactosidase (β-gal) under the control of the Lgr5 promoter, a stem/progenitor cell marker. In injured livers of Lgr5-LacZ mice, cells expressing β-galactosidase (β-gal) are considered as potential bipotent liver progenitors; however, their origin and identity remain unknown. Unexpectedly, using lineage tracing, we demonstrate that the β-gal+ cells do not originate from liver parenchymal cells. Instead, β-gal+ cells, isolated from injured livers of both Lgr5-LacZ and wild-type mice, are positive for markers of Kupffer cells, liver-resident macrophages. The β-gal expression in these cells is a result of elevated expression of the endogenous beta-galactosidase Glb1. In injured livers of Lgr5-LacZ mice, bacterial β-gal expression is very low, suggesting transgene silencing. The gene expression profile of the β-gal+ Kupffer cells from injured livers suggests a role in liver regeneration.

Keywords: Lgr5; Kupffer cells; TREM2; lineage tracing; liver; progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / adverse effects
  • Cell Lineage
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury / genetics*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism*
  • Lac Operon
  • Liver Regeneration
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Immunologic / metabolism*
  • Sequence Analysis, RNA
  • beta-Galactosidase / genetics*
  • beta-Galactosidase / metabolism


  • Escherichia coli Proteins
  • Lgr5 protein, mouse
  • Membrane Glycoproteins
  • Receptors, G-Protein-Coupled
  • Receptors, Immunologic
  • Trem2 protein, mouse
  • Carbon Tetrachloride
  • beta-Galactosidase