PMID- 17538966 OWN - NLM STAT- MEDLINE DCOM- 20070712 LR - 20191210 IS - 0270-9139 (Print) IS - 0270-9139 (Linking) VI - 45 IP - 6 DP - 2007 Jun TI - Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration. PG - 1462-70 AB - The experimental protocols used in the investigation of stem cell-mediated liver regeneration in rodents are characterized by activation of the hepatic stem cell compartment in the canals of Hering followed by transit amplification of oval cells and their subsequent differentiation along hepatic lineages. Although the protocols are numerous and often used interchangeably across species, a thorough comparative phenotypic analysis of oval cells in rats and mice using well-established and generally acknowledged molecular markers has not been provided. In the present study, we evaluated and compared the molecular phenotypes of oval cells in several of the most commonly used protocols of stem cell-mediated liver regeneration-namely, treatment with 2-acetylaminofluorene and partial (70%) hepatectomy (AAF/PHx); a choline-deficient, ethionine-supplemented (CDE) diet; a 3,5-diethoxycarbonyl-1,4-dihydro-collidin (DDC) diet; and N-acetyl-paraaminophen (APAP). Reproducibly, oval cells showing reactivity for cytokeratins (CKs), muscle pyruvate kinase (MPK), the adenosine triphosphate-binding cassette transporter ABCG2/BCRP1 (ABCG2), alpha-fetoprotein (AFP), and delta-like protein 1/preadipocyte factor 1 (Dlk/Pref-1) were induced in rat liver treated according to the AAF/PHx and CDE but not the DDC protocol. In mouse liver, the CDE, DDC, and APAP protocols all induced CKs and ABCG2-positive oval cells. However, AFP and Dlk/Pref-1 expression was rarely detected in oval cells. CONCLUSION: Our results delineate remarkable phenotypic discrepancies exhibited by oval cells in stem cell-mediated liver regeneration between rats and mice and underline the importance of careful extrapolation between individual species. FAU - Jelnes, Peter AU - Jelnes P AD - Danish Stem Cell Research Centre, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. FAU - Santoni-Rugiu, Eric AU - Santoni-Rugiu E FAU - Rasmussen, Morten AU - Rasmussen M FAU - Friis, Susanne Lunoe AU - Friis SL FAU - Nielsen, Jens Hoiriis AU - Nielsen JH FAU - Tygstrup, Niels AU - Tygstrup N FAU - Bisgaard, Hanne Cathrine AU - Bisgaard HC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Abcg2 protein, mouse) RN - 0 (Abcg2 protein, rat) RN - 0 (Biomarkers) RN - 0 (Calcium-Binding Proteins) RN - 0 (Dlk1 protein, mouse) RN - 0 (Dlk1 protein, rat) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - 0 (alpha-Fetoproteins) RN - 68238-35-7 (Keratins) RN - EC 2.7.1.40 (Pyruvate Kinase) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 2 MH - ATP-Binding Cassette Transporters/genetics/metabolism MH - Animals MH - Biomarkers/*metabolism MH - Calcium-Binding Proteins MH - Cell Lineage/physiology MH - Female MH - Immunohistochemistry MH - Intercellular Signaling Peptides and Proteins/genetics/metabolism MH - Keratins/metabolism MH - Liver/*cytology/*physiology MH - Liver Regeneration/*physiology MH - Male MH - Membrane Proteins/genetics/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Models, Animal MH - Phenotype MH - Pyruvate Kinase/genetics/metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Inbred F344 MH - Stem Cells/cytology/*physiology MH - alpha-Fetoproteins/genetics/metabolism EDAT- 2007/06/01 09:00 MHDA- 2007/07/13 09:00 CRDT- 2007/06/01 09:00 PHST- 2007/06/01 09:00 [pubmed] PHST- 2007/07/13 09:00 [medline] PHST- 2007/06/01 09:00 [entrez] AID - 10.1002/hep.21569 [doi] PST - ppublish SO - Hepatology. 2007 Jun;45(6):1462-70. doi: 10.1002/hep.21569.