Transcriptional Profiling of Cultured, Embryonic Epicardial Cells Identifies Novel Genes and Signaling Pathways Regulated by TGFR3 in vitro
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE75064 |
| Title | Transcriptional Profiling of Cultured, Embryonic Epicardial Cells Identifies Novel Genes and Signaling Pathways Regulated by TGFR3 in vitro |
| Description | The epicardium plays an important role in coronary vessel formation and Tgfbr3-/- mice exhibit failed coronary vessel development associated with decreased epicardial cell invasion. Immortalized Tgfbr3-/- epicardial cells display the same defects. Tgfbr3+/+ and Tgfbr3-/- cells incubated for 72 hours with VEH or ligands known to promote invasion via TGFR3 (TGF1, TGF2, BMP2), for 72 hours were harvested for RNA-seq analysis. We selected for genes >2-fold differentially expressed between Tgfbr3+/+ and Tgfbr3-/- cells when incubated with VEH (604), TGF1 (515), TGF2 (553), or BMP2 (632). Gene Ontology (GO) analysis of these genes identified dysregulated biological processes consistent with the defects observed in Tgfbr3-/- cells, including those associated with the extracellular matrix interaction. GO and Gene Regulatory Network (GRN) analysis identified distinct expression profiles between TGF1-TGF2 and VEH-BMP2 incubated cells, consistent with the differential response of epicardial cells to these ligands in vitro. Despite the differences observed between Tgfbr3+/+ and Tgfbr3-/- cells after TGF and BMP ligand addition, GRNs constructed from these gene lists identified NF-B as a key nodal point for all ligands examined. Tgfbr3-/- cells exhibited decreased expression of genes known to be activated by NF-B signaling. NF-B activity was stimulated in Tgfbr3+/+ epicardial cells after TGF2 or BMP2 incubation, while Tgfbr3-/- cells failed to activate NF-B in response to these ligands. Tgfbr3+/+ epicardial cells incubated with an inhibitor of NF-B signaling no longer invaded into a collagen gel in response to TGF2 or BMP2. These data suggest that NF-B signaling is dysregulated in Tgfbr3-/- epicardial cells and that NF-B signaling is required for epicardial cell invasion in vitro. Our approach successfully identified a signaling pathway important in epicardial cell behavior downstream of TGFR3. Overall, the genes and signaling pathways identified through our analysis yield the first comprehensive list of candidate genes whose expression is dependent on TGFR3 signaling. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75064 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE84085
Next Generation Sequencing Facilitates Quantitative Analysis of Human Primary and Pluripotent Stem Cell-Derived Epicardial Cell Transcriptomes
1
GSE87344
Lamin-B1 contributes to the proper timing of epicardial cell migration and function during heart development
1
GSE36778
Effect of Tgfbr2 disruption on gene expression in the aorta of Fbn1 wild-type and Fbn1C1039G mice
7
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
