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: Adam M. Passman, Jasmine Low, Roslyn London, Janina E. E. Tirnitz-Parker, Atsushi Miyajima, Minoru Tanaka, Helene Strick-Marchand, Gretchen J. Darlington, Megan Finch-Edmondson, Scott Ochsner, Cornelia Zhu, James Whelan, Bernard A. Callus, George C. T. Yeoh
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/5702873
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author Adam M. Passman
Jasmine Low
Roslyn London
Janina E. E. Tirnitz-Parker
Atsushi Miyajima
Minoru Tanaka
Helene Strick-Marchand
Gretchen J. Darlington
Megan Finch-Edmondson
Scott Ochsner
Cornelia Zhu
James Whelan
Bernard A. Callus
George C. T. Yeoh
author_facet Adam M. Passman
Jasmine Low
Roslyn London
Janina E. E. Tirnitz-Parker
Atsushi Miyajima
Minoru Tanaka
Helene Strick-Marchand
Gretchen J. Darlington
Megan Finch-Edmondson
Scott Ochsner
Cornelia Zhu
James Whelan
Bernard A. Callus
George C. T. Yeoh
author_sort Adam M. Passman
collection DOAJ
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 doaj-art-b0dfd949a72441b68d7de746f42adaad2025-08-20T02:23:34ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/57028735702873A Transcriptomic Signature of Mouse Liver Progenitor CellsAdam M. Passman0Jasmine Low1Roslyn London2Janina E. E. Tirnitz-Parker3Atsushi Miyajima4Minoru Tanaka5Helene Strick-Marchand6Gretchen J. Darlington7Megan Finch-Edmondson8Scott Ochsner9Cornelia Zhu10James Whelan11Bernard A. Callus12George C. T. Yeoh13School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, AustraliaSchool of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, AustraliaSchool of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, AustraliaSchool of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, AustraliaInstitute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-8654, JapanInstitute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-8654, JapanUnité de Génétique de la Différenciation, Institut Pasteur, 75015 Paris, FranceHuffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USADepartment of Physiology, NUS Yong Loo Lin School of Medicine, 117411, SingaporeDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USASchool of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, AustraliaARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, Crawley, WA 6009, AustraliaSchool of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, AustraliaSchool of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, AustraliaLiver 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.http://dx.doi.org/10.1155/2016/5702873
spellingShingle Adam M. Passman
Jasmine Low
Roslyn London
Janina E. E. Tirnitz-Parker
Atsushi Miyajima
Minoru Tanaka
Helene Strick-Marchand
Gretchen J. Darlington
Megan Finch-Edmondson
Scott Ochsner
Cornelia Zhu
James Whelan
Bernard A. Callus
George C. T. Yeoh
A Transcriptomic Signature of Mouse Liver Progenitor Cells
Stem Cells International
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://dx.doi.org/10.1155/2016/5702873
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