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Title: Systematic analysis of time resolved transcriptional signature of the cross-talk between HGF and IL-6 refines the role of Cxcl10 in hepatocyte proliferation control      
dateReleased:
06-01-2016
description:
Liver regeneration is characterized by a scheduled sequence of inner and intra-cellular signaling events. It starts with an initial inflammatory phase, followed by a period of rapidly proliferating hepatocytes and stopping abruptly when the liver mass is restored. The cytokines hepatocellular growth factor (HGF) and interleukin 6 (IL-6) play a pivotal role during this process with the former driving proliferation that is enhanced by the latter. While the individual importance of HGF and IL6 has been studied comprahensively the role of cross-talk in control of hepatic proliferation is jet largely unknown. To this end, we performed time-resolved transcriptional profiling of of murine hepatocytes stimulated with HGF and IL-6 indiviually as well as in combination. Thorough systematic investigation performing statistical analysis, mathematical formalization of cross-talk effects on the transcriptional level as well as gene-regulatory network inference revealed the transcriptional program of the cross-talk initiated by HGF and IL-6. Using the proliferation associated Hepcidin (Hamp) and Amphiregulin (Areg) as marker genes for liver regeneration we perform exthensive in-silico experiments with the inferred gene-regulatory network for the identification of the most important players in regulation of the proliferation process. Among other genes, this predicted chemokine (C-X-C motif) ligand 10 (Cxcl10) as an important factor in the temporal regulation of proliferation. These predictions were validated by independent in vitro expression data as well as independent in vivo literature data. While Cxcl10 is known to be involved in liver regeneration, our study extend its role towards its temporal orchestration. Cells were stimulated with either 40 ng/ml rmHGF (all R&D Systems) or 40 ng/ml rhIL-6 alone or in combination. Cells were left untreated as unstimulated control. RNA from three biological triplicates was extracted at 0, 0.5, 2, 4, 8, 16, 24 and 32 hours after stimulation using the RNeasy Mini Plus Kit (Qiagen, Hilden, Germany).
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-69928
refinement:
raw
alternateIdentifiers:
69928
keywords:
functional genomics
dateModified:
06-04-2016
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-AFFY-45
name:
Affymetrix GeneChip Mouse Genome 430 2.0 [Mouse430_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-69928/E-GEOD-69928.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-69928/E-GEOD-69928.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69928
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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