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A Transcriptomic Signature of Mouse Liver Progenitor Cells

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journal contribution
posted on 09.05.2022, 00:56 authored by AM Passman, J Low, R London, JEE Tirnitz-Parker, A Miyajima, M Tanaka, H Strick-Marchand, GJ Darlington, M Finch-Edmondson, S Ochsner, C Zhu, James WhelanJames Whelan, BA Callus, GCT Yeoh
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.

Funding

This work was supported by the Australian Research Council Centre of Excellence Grant (CE056149), the Cancer Council of Western Australia (IDs 634424, APP1010749, and APP1067515), the National Health and Medical Research Council Project Grant (APP1042368), and the Association of International Cancer Research (no. 09-0084).

History

Publication Date

01/01/2016

Journal

Stem Cells International

Volume

2016

Article Number

5702873

Pagination

15p. (p. 1-15)

Publisher

Hindawi Publishing Corporation

ISSN

1687-9678

Rights Statement

© 2016 Adam M. Passman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.