Transcriptomic analyses of mouse liver progenitor cells: establishing their signature and defining gene expression patterns associated with neoplastic transformation

Jasmine Low

Research output: ThesisDoctoral Thesis

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Abstract

Liver progenitor cells are a subpopulation of liver cells with bipotentiality, that is, they have the ability to differentiate into hepatocytes or cholangiocytes. In certain circumstances, such as chronic liver disease, they are able to repopulate damaged livers and have become the centre of interest for cell-based liver regeneration. However, upon injection of these cells into rodents, some progenitor cell lines form tumours and this brings to light their potential association with liver carcinogenesis. The overall aim of this study was to establish gene expression profiles for tumorigenic and non-tumorigenic progenitor cells in order to better understand molecular changes which characterise each group. The ability to distinguish these populations will greatly assist in strategies to realise the therapeutic potential of liver progenitor cells. A transcriptomic approach was taken to investigate liver progenitor cell culture models and gene expression microarrays were performed to compare several different cell lines. Public microarrays were also downloaded and incorporated into the study, including some performed on embryonic stem cells, adult liver tissues and hepatocellular carcinoma-related tissues, collectively encompassing 405 microarrays experiments. Pathway analyses showed liver progenitor cells have many upregulated pathways compared to liver parenchymal cells, especially those governing the cell cycle, Wnt, TGF-beta, MAPK and ErbB signaling. In addition, purine and pyrimidine metabolism pathways were upregulated in all the 'immortalised' cell lines. Based on key transcript expression patterns that correlated highly with the expression patterns of known liver progenitor cell markers, a list of 32 novel, potential markers of liver progenitor cells was identified. Additionally, the availability of a combination of tumorigenic and non-tumorigenic liver progenitor cell lines allowed us to focus on their differences and these were projected onto chromosome
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2010

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