Abstract
Background and aims. Liver progenitor cells (LPCs) have been extensively investigated because of their capacity to differentiate into hepatocytes or cholangiocytes during sever acute and chonic liver injury. Currently, there is much debate whether these cells significantly contribute to liver regeneration, partly due to the lack of an exact identity. Different ‘specific’ LPC markers (Foxl1, LGR5, HNF1b, MIC1C3, EpCAM) have been used to isolate and characterize LPCs from healthy, damaged and regenerating livers. Whether these studies are actually working with the same cells has never been established. Our aim was to obtain a unique LPC gene signature by comparing the expression profiles of recently published array data on LPCs using Foxl1, LGR5, MIC1C3 and HNF1b as markers.
Methods. We compared LPC gene expression data which was published within the last 5 years (Foxl1, Shin et al., GSE28892; LGR5, Huch et al., GSE32210; MIC1C3, Dorrell et al., GSE29121; HNF1b, Rodrigo-Torres et al.). First, our focus was based on gene expression in LPCs that were at least 2 fold increased, using MIC1C3 and HNF1b markers as representative LPC markers in healthy livers. Second, we looked at genes that were 2 times or more upregulated during activation using DDC (MIC1C3, HNF1b), CDE (HNF1b) or CCl4 (LGR5) diet.
Results. More than 600 genes were highly expressed in LPCs and are associated with different gene ontologies, like system development, cell differentiation, tissue development and organ development. Interestingly, KEGG pathways show high significance in Hippo signalling pathway, PI3K-Akt signalling pathway and ECM-receptor interaction. Many of these genes are therefore possible markers and need to be further investigated. Only 3 genes were upregulated during LPC activation in all experimental settings and all isolation methods, indicating that these could be robust markers of LPC activation.
Conclusion. Our analysis shows major difference between all expression profiles of the differently identified LPCs. While there is an overlap in gene expression between these “different” LPCs, only 3 genes seem to differentially expressed in all LPCs upon activation and not in surrounding liver cells. Progress on the validation of these 3 genes as key markers of LPC activation using additional injury settings and LPC isolations will be presented.
Methods. We compared LPC gene expression data which was published within the last 5 years (Foxl1, Shin et al., GSE28892; LGR5, Huch et al., GSE32210; MIC1C3, Dorrell et al., GSE29121; HNF1b, Rodrigo-Torres et al.). First, our focus was based on gene expression in LPCs that were at least 2 fold increased, using MIC1C3 and HNF1b markers as representative LPC markers in healthy livers. Second, we looked at genes that were 2 times or more upregulated during activation using DDC (MIC1C3, HNF1b), CDE (HNF1b) or CCl4 (LGR5) diet.
Results. More than 600 genes were highly expressed in LPCs and are associated with different gene ontologies, like system development, cell differentiation, tissue development and organ development. Interestingly, KEGG pathways show high significance in Hippo signalling pathway, PI3K-Akt signalling pathway and ECM-receptor interaction. Many of these genes are therefore possible markers and need to be further investigated. Only 3 genes were upregulated during LPC activation in all experimental settings and all isolation methods, indicating that these could be robust markers of LPC activation.
Conclusion. Our analysis shows major difference between all expression profiles of the differently identified LPCs. While there is an overlap in gene expression between these “different” LPCs, only 3 genes seem to differentially expressed in all LPCs upon activation and not in surrounding liver cells. Progress on the validation of these 3 genes as key markers of LPC activation using additional injury settings and LPC isolations will be presented.
Original language | English |
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Publication status | Published - 13 Apr 2016 |
Event | EASL The International Liver Congress 2016 - Fira Barcelona Gran Via, Barclona, Spain Duration: 13 Apr 2016 → 17 Apr 2016 |
Conference
Conference | EASL The International Liver Congress 2016 |
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Country/Territory | Spain |
City | Barclona |
Period | 13/04/16 → 17/04/16 |