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Identification and expansion of a unique stem cell population from adult mouse gallbladder.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2011 Nov; Vol. 54 (5), pp. 1830-41. - Publication Year :
- 2011
-
Abstract
- Unlabelled: The identification of resident stem cells in the mouse gallbladder is, to date, unexplored. In addition, the relationship between adult gallbladder stem cells and intrahepatic bile duct (IHBD) cells is not well understood. The aim of this study was to isolate stem cells from an adult mouse gallbladder and determine whether they were unique, compared to IHBD cells. By limiting dilution analyses and index sorts, we found that an EpCAM(+) CD49f(hi) epithelial cell subpopulation from primary gallbladder is enriched in colony-forming cells, compared to EpCAM(+) CD49f(lo) cells. EpCAM(+) CD49f(hi) cells expressed cluster of differentiation (CD)29, CD133, and stem cell antigen-1, but were negative for lineage markers CD31, CD45, and F4/80. Using a novel feeder cell-culture system, we observed long-term (>passage 20) and clonal expansion of the EpCAM(+) CD49f(hi) cells in vitro. In a matrigel differentiation assay, EpCAM(+) CD49f(+) cells expanding in vitro underwent organotypic morphogenesis forming ductular structures and cysts. These structures are similar to, and recapitulate a transport function of, primary gallbladder. EpCAM(+) CD49f(+) cells also engraft into the subcutaneous space of recipient mice. We compared primary gallbladder and IHBD cells by flow cytometry and found phenotypic differences in the expression of CD49f, CD49e, CD81, CD26, CD54, and CD166. In addition, oligonucleotide microarrays showed that the expanded EpCAM(+) CD49f(+) gallbladder cells and IHBD cells exhibit differences related to lipid and drug metabolism. Notable genes that were different are cytochrome P450, glutathione S-transferase, Indian hedgehog, and solute carrier family genes.<br />Conclusion: We have isolated an epithelial cell population from primary mouse gallbladder with stem cell characteristics and found it to be unique, compared to IHBD cells.<br /> (Copyright © 2011 American Association for the Study of Liver Diseases.)
- Subjects :
- Adult Stem Cells metabolism
Age Factors
Animals
Antigens, Neoplasm metabolism
Bile Ducts, Intrahepatic cytology
Biomarkers metabolism
Cell Adhesion Molecules metabolism
Cell Differentiation physiology
Cell Separation methods
Cells, Cultured
Epithelial Cell Adhesion Molecule
Epithelial Cells cytology
Epithelial Cells metabolism
Green Fluorescent Proteins genetics
Integrin alpha6 metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Adult Stem Cells cytology
Gallbladder cytology
Stem Cell Niche physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 54
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 21793026
- Full Text :
- https://doi.org/10.1002/hep.24568