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Our goal was to identify an enriched population of bipotent oval cells using a combination of flow cytometry and single cell gene expression in conjunction with lineage-specific liver injury models. Expression of cell surface markers on nonparenchymal, nonhematopoietic (CD45\u2212) cells were characterized. Cell populations were isolated by flow cytometry for gene expression studies. 3,5-Diethoxycarbonyl-1,4-dihydrocollidine toxic injury induced cell cycling and expansion specifically in the subpopulation of oval cells in the periportal zone that express CD133. CD133+CD45\u2212 cells expressed hepatoblast and stem cell-associated genes, and single cells coexpressed both hepatocyte and cholangiocyte-associated genes, indicating bilineage potential. CD133+CD45\u2212 cells proliferated in response to liver injury. Following toxic hepatocyte damage, CD133+CD45\u2212 cells demonstrated upregulated expression of the hepatocyte gene Albumin. In contrast, toxic cholangiocyte injury resulted in upregulation of the cholangiocyte gene Ck19. After 21\u201328 days in culture, CD133+CD45\u2212 cells continued to generate cells of both hepatocyte and cholangiocyte lineages. Thus, CD133 expression identifies a population of oval cells in adult murine liver with the gene expression profile and function of primitive, bipotent liver stem cells. In response to lineage-specific injury, these cells demonstrate a lineage-appropriate genetic response. Disclosure of potential conflicts of interest is found at the end of this article.<\/jats:p>","DOI":"10.1634\/stemcells.2007-0176","type":"journal-article","created":{"date-parts":[[2007,6,22]],"date-time":"2007-06-22T01:59:25Z","timestamp":1182477565000},"page":"2419-2429","source":"Crossref","is-referenced-by-count":121,"title":["A CD133-Expressing Murine Liver Oval Cell Population with Bilineage Potential"],"prefix":"10.1093","volume":"25","author":[{"given":"C. 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