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Series GSE121697 Query DataSets for GSE121697
Status Public on Oct 24, 2018
Title Epidermal growth factor activates β-catenin via integrin-linked kinase to control proliferation of mesenchymal stromal cells.
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Mesenchymal stromal cells (MSCs) are located in bone marrow where they help to maintain bone homeostasis and repair through the ability to expand in response to mitotic stimuli and differentiate into skeletal linages. The signalling mechanisms that enable precise control of MSC function remain unclear. Here, we have identified a non-canonical epidermal growth factor (EGF) signalling pathway in MSCs, which acts via integrin-linked kinase (ILK) to activate β-catenin, a key component of Wnt signalling. EGF induces nuclear translocation of β-catenin in MSCs but does not drive T cell factor (TCF)-mediated transactivation of Wnt target genes, and we demonstrate by Design of Experiments statistical analysis that the EGF/β-catenin and Wnt/β-catenin pathways do not cross-talk following co-stimulation with multiple concentrations of both ligands. By examining EGF-regulated genes in MSCs by RNA-Sequencing, we identified gene sets that were exclusively regulated by the EGF/b-catenin pathway, which were distinct from canonical EGF-regulated genes. In contrast, the expression of subsets of canonical EGF signalling gene targets were significantly influenced by b-catenin activation. These newly-identified EGF signalling pathways cooperate to enable EGF-mediated proliferation of MSCs by alleviating the suppression of cell cycle pathways induced by canonical EGF signalling.
Overall design Examination of expression profiles of 3 samples of untreated MSCs, 3 samples EGF treated, 3 samples EGF + IWR-1 treated MSCs using RNA-seq analysis
Contributor(s) Genever P, Knight C, James S, Kuntin D, Fox J, Newling K, Hollings S, Pennock R
Citation(s) 30287279
Submission date Oct 23, 2018
Last update date Dec 23, 2018
Contact name Katherine Newling
Phone +44 (01904) 328767
Organization name University of York
Department Biology
Street address Wentworth Way
City York
ZIP/Postal code YO10 5DD
Country United Kingdom
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (9)
GSM3444209 untreated_S01
GSM3444210 untreated_S02
GSM3444211 untreated_S03
BioProject PRJNA498109
SRA SRP166560

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Supplementary file Size Download File type/resource
GSE121697_Cufflinks_FPKMs_and_TukeyHSD_results.txt.gz 3.1 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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