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Series GSE69928 Query DataSets for GSE69928
Status Public on Jun 01, 2016
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
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
Overall design 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).
Contributor(s) Hoppe A, Vlaic S, Mueller N, Braun S, Meyer R, Bonefas S, D'Allesandro L, Müller S, Gretz N, Klingmüller U, Boerries M, Busch H
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Submission date Jun 16, 2015
Last update date Feb 11, 2019
Contact name Hauke Busch
Phone +49-451-3101-8470
Organization name University of Lübeck
Department Lübeck Institute of Experimental Dermatology
Street address Ratzeburger Allee 160
City Lübeck
State/province Schleswig-Holstein
ZIP/Postal code 23538
Country Germany
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (60)
GSM1713208 Hepatocytes-Ctl-0h-rep1
GSM1713209 Hepatocytes-Ctl-0h-rep2
GSM1713210 Hepatocytes-Ctl-0h-rep3
This SubSeries is part of SuperSeries:
GSE69939 Cross-talk of Il6 and HGF in the inflammation and proliferation response of primary murine hepatocytes
BioProject PRJNA287157

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE69928_RAW.tar 205.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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