Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Hepatocyte ductal metaplasia in chronic mouse liver injury

ABSTRACT: Expression profiling of hepatocytes-derived ductal cells with properties intermediate between mature hepatocytes and cholangiocytes. Chimeric adult mice were generated where mature hepatocytes were marked with a fluorescent red marker. Chronic injury was induced for ~6weeks and three cell types were isolated by FACS (Influx, BD) for expression analysis by RNAseq based on cell surface phenotype and origin: hepatocytes (n=3), hepatocyte-derived oval cells (1c3+, n=5), and cholangiocyte-derived oval cells (1c3+, n=5).

ORGANISM(S): Mus musculus

SUBMITTER: Branden Tarlow

PROVIDER: E-GEOD-55552 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes.

Tarlow Branden D BD Pelz Carl C Naugler Willscott E WE Wakefield Leslie L Wilson Elizabeth M EM Finegold Milton J MJ Grompe Markus M

Cell stem cell 20141009 5

Adult liver progenitor cells are biliary-like epithelial cells that emerge only under injury conditions in the periportal region of the liver. They exhibit phenotypes of both hepatocytes and bile ducts. However, their origin and their significance to injury repair remain unclear. Here, we used a chimeric lineage tracing system to demonstrate that hepatocytes contribute to the progenitor pool. RNA-sequencing, ultrastructural analysis, and in vitro progenitor assays revealed that hepatocyte-derive ...[more]

PMID: 25312494

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Project description:The ability to purify to homogeneity a population of hepatic progenitor cells from adult liver is critical for their characterization prior to any therapeutic application. As a step in this direction, we have utilized gene profiling of a bipotential liver cell line from dpc 14 mouse embryonic liver to catalog genes expressed by liver progenitor cells. These cells, known as Bipotential Mouse Embryonic Liver (BMEL) cells, proliferate in an undifferentiated state and are capable of differentiating into hepatocyte-like and cholangiocyte-like cells in vitro. Upon transplantation, BMEL cells are capable of differentiating into hepatocytes and cholangiocytes in vivo. Microarray analysis of gene expression in the 9A1 and 14B3 BMEL cell lines grown under proliferating and differentiating conditions was used to identify cell surface markers preferentially expressed in the bipotential undifferentiated state. This analysis revealed that proliferating BMEL cells express many genes involved in cell cycle regulation whereas differentiation of BMEL cells by cell aggregation causes a switch in gene expression to functions characteristic of mature hepatocytes. In addition, microarray data and protein analysis indicated that the Notch signaling pathway could be involved in maintaining BMEL cells in an undifferentiated stem cell state. Using GO annotation, a list of cell surface markers preferentially expressed on undifferentiated BMEL cells was generated. One marker, Cd24a, is specifically expressed on progenitor oval cells in livers of DDC treated animals. We therefore consider Cd24a expression a candidate molecule for purification of hepatic progenitor cells. Experiment Overall Design: RNA was extracted from two independently isolated BMEL cell lines (9A1 and 14B3) after culture under three conditions (basal, aggregate 1 day, and aggregate 5 days). Duplicate biological replicates were collected for each cell line:culture condition combination for a total of 12 samples. Samples were biotin-labeled, hybridized to mouse 430 2.0 chips, and scanned according to established Affymetrix protocols.

Project description:The ability to purify to homogeneity a population of hepatic progenitor cells from adult liver is critical for their characterization prior to any therapeutic application. As a step in this direction, we have utilized gene profiling of a bipotential liver cell line from dpc 14 mouse embryonic liver to catalog genes expressed by liver progenitor cells. These cells, known as Bipotential Mouse Embryonic Liver (BMEL) cells, proliferate in an undifferentiated state and are capable of differentiating into hepatocyte-like and cholangiocyte-like cells in vitro. Upon transplantation, BMEL cells are capable of differentiating into hepatocytes and cholangiocytes in vivo. Microarray analysis of gene expression in the 9A1 and 14B3 BMEL cell lines grown under proliferating and differentiating conditions was used to identify cell surface markers preferentially expressed in the bipotential undifferentiated state. This analysis revealed that proliferating BMEL cells express many genes involved in cell cycle regulation whereas differentiation of BMEL cells by cell aggregation causes a switch in gene expression to functions characteristic of mature hepatocytes. In addition, microarray data and protein analysis indicated that the Notch signaling pathway could be involved in maintaining BMEL cells in an undifferentiated stem cell state. Using GO annotation, a list of cell surface markers preferentially expressed on undifferentiated BMEL cells was generated. One marker, Cd24a, is specifically expressed on progenitor oval cells in livers of DDC treated animals. We therefore consider Cd24a expression a candidate molecule for purification of hepatic progenitor cells. Experiment Overall Design: RNA was extracted from two independently isolated BMEL cell lines (9A1 and 14B3) after culture under three conditions (basal, aggregate 5 days, and Matrigel). Duplicate biological replicates were collected for each cell line:culture condition combination for a total of 12 samples. Samples were biotin-labeled, hybridized to mouse 430a chips, and scanned according to established Affymetrix protocols.

Dataset Information

Hepatocyte ductal metaplasia in chronic mouse liver injury

Publications

Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes.

Similar Datasets

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