Endogenous beta-galactosidase activity marks a TREM2-expressing Kupffer cell population in injured livers of Lgr5-LacZ and wild-type mice
Publication date
2020-03
Authors
Klaas, Mariliis
Mäemets-Allas, Kristina
Lõhmussaar, Kadi
Tooming, Mikk
Viil, Janeli
Jaks, Viljar
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Advisors
Supervisors
Document Type
Article
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License
taverne
Abstract
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
Animals, Carbon Tetrachloride/adverse effects, Cell Lineage, Cells, Cultured, Chemical and Drug Induced Liver Injury/genetics, Escherichia coli Proteins/genetics, Escherichia coli/enzymology, Female, Gene Expression Profiling, Gene Expression Regulation, Enzymologic, Kupffer Cells/drug effects, 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, Taverne, Journal Article, Research Support, Non-U.S. Gov't
Citation
Klaas, M, Mäemets-Allas, K, Lõhmussaar, K, Tooming, M, Viil, J & Jaks, V 2020, 'Endogenous beta-galactosidase activity marks a TREM2-expressing Kupffer cell population in injured livers of Lgr5-LacZ and wild-type mice', FEBS letters, vol. 594, no. 5, pp. 958-970. https://doi.org/10.1002/1873-3468.13669