Endogenous beta-galactosidase activity marks a TREM2-expressing Kupffer cell population in injured livers of Lgr5-LacZ and wild-type mice
Klaas, Mariliis; Mäemets-Allas, Kristina; Lõhmussaar, Kadi; Tooming, Mikk; Viil, Janeli; Jaks, Viljar
(2020) FEBS letters, volume 594, issue 5, pp. 958 - 970
(Article)
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
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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.
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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, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 0014-5793
Publisher: Elsevier
Note: Funding Information: We thank Vladimir Benes, Dinko Pavlinic and Bettina Haase from EMBL for performing the RNASeq and transcript mapping, as well as Guoqiang Gu and Cedric Blanpain for the K19CreERT2 mice. We are also grateful to Dmitri Lubenets for technical assistance. This work was supported by the EMBO Installation Grant No 1819 and grants PUT4 and PRG057 from the Estonian Research Council. Funding Information: We thank Vladimir Benes, Dinko Pavlinic and Bettina Haase from EMBL for performing the RNASeq and transcript mapping, as well as Guoqiang Gu and Cedric Blanpain for the K19CreERT2 mice. We are also grateful to Dmitri Lubenets for technical assistance. This work was supported by the EMBO Installation Grant No 1819 and grants PUT4 and PRG057 from the Estonian Research Council. Publisher Copyright: © 2019 Federation of European Biochemical Societies
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