TY - JOUR
T1 - Endogenous beta-galactosidase activity marks a TREM2-expressing Kupffer cell population in injured livers of Lgr5-LacZ and wild-type mice
AU - Klaas, Mariliis
AU - Mäemets-Allas, Kristina
AU - Lõhmussaar, Kadi
AU - Tooming, Mikk
AU - Viil, Janeli
AU - Jaks, Viljar
N1 - 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
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Animals
KW - Carbon Tetrachloride/adverse effects
KW - Cell Lineage
KW - Cells, Cultured
KW - Chemical and Drug Induced Liver Injury/genetics
KW - Escherichia coli Proteins/genetics
KW - Escherichia coli/enzymology
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Enzymologic
KW - Kupffer Cells/drug effects
KW - Lac Operon
KW - Liver Regeneration
KW - Male
KW - Membrane Glycoproteins/metabolism
KW - Mice
KW - Mice, Transgenic
KW - Receptors, G-Protein-Coupled/genetics
KW - Receptors, Immunologic/metabolism
KW - Sequence Analysis, RNA
KW - beta-Galactosidase/genetics
UR - http://www.scopus.com/inward/record.url?scp=85075737505&partnerID=8YFLogxK
U2 - 10.1002/1873-3468.13669
DO - 10.1002/1873-3468.13669
M3 - Article
C2 - 31705801
AN - SCOPUS:85075737505
SN - 0014-5793
VL - 594
SP - 958
EP - 970
JO - FEBS letters
JF - FEBS letters
IS - 5
ER -