title: The canine hepatic progenitor cell niche: molecular characterisation in health and disease.
abstract: Hepatic progenitor cells (HPCs) are an adult stem cell compartment in the liver that contributes to liver regeneration when replication of mature hepatocytes is insufficient. In this study, laser microdissection was used to isolate HPC niches from the livers of healthy dogs and dogs with lobular dissecting hepatitis (LDH), in which HPCs are massively activated. Gene expression of HPC, hepatocyte and biliary markers was determined by quantitative reverse transcriptase PCR. Expression and localisation of selected markers were further studied at the protein level by immunohistochemistry and immunofluorescent double staining in samples of normal liver and liver from dogs with LDH, acute and chronic hepatitis, and extrahepatic cholestasis. Activated HPC niches had higher gene expression of the hepatic progenitor markers OPN, FN14, CD29, CD44, CD133, LIF, LIFR and BMI1 compared to HPCs from normal liver. There was lower expression of albumin, but activated HPC niches were positive for the biliary markers SOX9, HNF1β and keratin 19 by immunohistochemistry and immunofluorescence. Laminin, activated stellate cells and macrophages are abundant extracellular matrix and cellular components of the canine HPC niche. This study demonstrates that the molecular and cellular characteristics of canine HPCs are similar to rodent and human HPCs, and that canine HPCs are distinctively activated in different types of liver disease.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: H S
authors.initials: HS
authors.lastname: Kruitwagen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Spee
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: C S
authors.initials: CS
authors.lastname: Viebahn
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: H B
authors.initials: HB
authors.lastname: Venema
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: L C
authors.initials: LC
authors.lastname: Penning
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: G C M
authors.initials: GC
authors.lastname: Grinwis
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Favier
authors.affiliation: TCCI Consultancy BV, Utrecht, The Netherlands.
authors.forename: T S G A M
authors.initials: TS
authors.lastname: van den Ingh
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Rothuizen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands. Electronic address: b.a.schotanus@uu.nl.
authors.forename: B A
authors.initials: BA
authors.lastname: Schotanus
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004283:Dog Diseases / Q000235:genetics / Q000628:therapy*; D004285:Dogs; D005786:Gene Expression Regulation; D006520:Hepatitis, Animal / Q000628:therapy*; D007150:Immunohistochemistry / Q000662:veterinary; D008099:Liver / Q000166:cytology*; D042282:Microdissection / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D033581:Stem Cell Transplantation / Q000662:veterinary*; D013234:Stem Cells / Q000502:physiology*
chemical_list: D015415:Biomarkers
keywords: Canine; Gene expression; Hepatic progenitor cell; Laser microdissection; Liver; Protein expression