A Transcriptomic Signature of Mouse Liver Progenitor Cells

Liver progenitor cells (LPCs) can proliferate extensively, are able to differentiate into hepatocytes and cholangiocytes, and contribute to liver regeneration. The presence of LPCs, however, often accompanies liver disease and hepatocellular carcinoma (HCC), indicating that they may be a cancer stem...

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Main Authors: Passman, A., Low, J., London, R., Tirnitz-Parker, Nina, Miyajima, A., Tanaka, M., Strick-Marchand, H., Darlington, G., Finch-Edmondson, M., Ochsner, S., Zhu, C., Whelan, J., Callus, B., Yeoh, G.
Format: Journal Article
Published: 2016
Online Access:http://hdl.handle.net/20.500.11937/45175
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author Passman, A.
Low, J.
London, R.
Tirnitz-Parker, Nina
Miyajima, A.
Tanaka, M.
Strick-Marchand, H.
Darlington, G.
Finch-Edmondson, M.
Ochsner, S.
Zhu, C.
Whelan, J.
Callus, B.
Yeoh, G.
author_facet Passman, A.
Low, J.
London, R.
Tirnitz-Parker, Nina
Miyajima, A.
Tanaka, M.
Strick-Marchand, H.
Darlington, G.
Finch-Edmondson, M.
Ochsner, S.
Zhu, C.
Whelan, J.
Callus, B.
Yeoh, G.
author_sort Passman, A.
building Curtin Institutional Repository
collection Online Access
description Liver progenitor cells (LPCs) can proliferate extensively, are able to differentiate into hepatocytes and cholangiocytes, and contribute to liver regeneration. The presence of LPCs, however, often accompanies liver disease and hepatocellular carcinoma (HCC), indicating that they may be a cancer stem cell. Understanding LPC biology and establishing a sensitive, rapid, and reliable method to detect their presence in the liver will assist diagnosis and facilitate monitoring of treatment outcomes in patients with liver pathologies. A transcriptomic meta-analysis of over 400 microarrays was undertaken to compare LPC lines against datasets of muscle and embryonic stem cell lines, embryonic and developed liver (DL), and HCC. Three gene clusters distinguishing LPCs from other liver cell types were identified. Pathways overrepresented in these clusters denote the proliferative nature of LPCs and their association with HCC. Our analysis also revealed 26 novel markers, LPC markers, including Mcm2 and Ltbp3, and eight known LPC markers, including M2pk and Ncam. These markers specified the presence of LPCs in pathological liver tissue by qPCR and correlated with LPC abundance determined using immunohistochemistry. These results showcase the value of global transcript profiling to identify pathways and markers that may be used to detect LPCs in injured or diseased liver.
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spelling curtin-20.500.11937-451752017-09-13T14:20:15Z A Transcriptomic Signature of Mouse Liver Progenitor Cells Passman, A. Low, J. London, R. Tirnitz-Parker, Nina Miyajima, A. Tanaka, M. Strick-Marchand, H. Darlington, G. Finch-Edmondson, M. Ochsner, S. Zhu, C. Whelan, J. Callus, B. Yeoh, G. Liver progenitor cells (LPCs) can proliferate extensively, are able to differentiate into hepatocytes and cholangiocytes, and contribute to liver regeneration. The presence of LPCs, however, often accompanies liver disease and hepatocellular carcinoma (HCC), indicating that they may be a cancer stem cell. Understanding LPC biology and establishing a sensitive, rapid, and reliable method to detect their presence in the liver will assist diagnosis and facilitate monitoring of treatment outcomes in patients with liver pathologies. A transcriptomic meta-analysis of over 400 microarrays was undertaken to compare LPC lines against datasets of muscle and embryonic stem cell lines, embryonic and developed liver (DL), and HCC. Three gene clusters distinguishing LPCs from other liver cell types were identified. Pathways overrepresented in these clusters denote the proliferative nature of LPCs and their association with HCC. Our analysis also revealed 26 novel markers, LPC markers, including Mcm2 and Ltbp3, and eight known LPC markers, including M2pk and Ncam. These markers specified the presence of LPCs in pathological liver tissue by qPCR and correlated with LPC abundance determined using immunohistochemistry. These results showcase the value of global transcript profiling to identify pathways and markers that may be used to detect LPCs in injured or diseased liver. 2016 Journal Article http://hdl.handle.net/20.500.11937/45175 10.1155/2016/5702873 fulltext
spellingShingle Passman, A.
Low, J.
London, R.
Tirnitz-Parker, Nina
Miyajima, A.
Tanaka, M.
Strick-Marchand, H.
Darlington, G.
Finch-Edmondson, M.
Ochsner, S.
Zhu, C.
Whelan, J.
Callus, B.
Yeoh, G.
A Transcriptomic Signature of Mouse Liver Progenitor Cells
title A Transcriptomic Signature of Mouse Liver Progenitor Cells
title_full A Transcriptomic Signature of Mouse Liver Progenitor Cells
title_fullStr A Transcriptomic Signature of Mouse Liver Progenitor Cells
title_full_unstemmed A Transcriptomic Signature of Mouse Liver Progenitor Cells
title_short A Transcriptomic Signature of Mouse Liver Progenitor Cells
title_sort transcriptomic signature of mouse liver progenitor cells
url http://hdl.handle.net/20.500.11937/45175