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SRP078053
Homo sapiens
18 Downloadable Samples
Illumina HiSeq 1500
Description
The epithelial-mesenchymal transition (EMT) is a multistep dedifferentiation program important in tissue repair. Here, we examined the role of the transcriptional regulator NFkB in EMT of human primary small airway epithelial cells (hSAECs). Surprisingly, transforming growth factor ß (TGFß) activated NFkB/RELA proto-oncogene, NFkB subunit (RELA) translocation within 1 day of stimulation, yet induction of its downstream gene regulatory network occurred only after 3 days. A time course of TGFß-induced EMT transition was analyzed by RNA-Seq in the absence or presence of inducible shRNA-mediated silencing of RELA. In WT cells, TGFß stimulation significantly affected the expression of 2,441 genes. Gene set enrichment analysis identified Wnt, cadherin, and NFkB signaling as the most prominent TGFß-inducible pathways. By comparison, RELA controlled expression of 3,138 overlapping genes mapping to Wnt, cadherin, and chemokine signaling pathways. Conducting upstream regulator analysis, we found that RELA controls six clusters of upstream transcription factors, many of which overlapped with a transcription factor topology map of EMT developed earlier. RELA triggered expression of three key EMT pathways: (1) the Wnt/ß-catenin morphogen pathway, (2) the JUN transcription factor, and (3) the Snail family transcriptional repressor 1 (SNAI1). RELA binding to target genes was confirmed by ChIP. Experiments independently validating Wnt dependence on RELA were performed by silencing RELA via genome editing and indicated that TGFß-induced WNT5B expression and downstream activation of the Wnt target AXIN2 are RELA-dependent. We conclude that RELA is a master transcriptional regulator of EMT upstream of Wnt morphogen, JUN, SNAI1-ZEB1, and interleukin-6 autocrine loops. Overall design: RNA-seq transcriptome profiling of TGF-Beta stimulated RelA wildtype and knock-down cells
Publication Title
The NFκB subunit RELA is a master transcriptional regulator of the committed epithelial-mesenchymal transition in airway epithelial cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 1000
Description
The airway epithelial cell plays a central role in coordinating pulmonary response to injury and inflammation. Here, transforming growth factor-b (TGFb) activates gene expression programs to induce stem cell-like properties, inhibit expression of differentiated epithelial adhesion proteins and express mesenchymal contractile proteins. This process is known as epithelial mesenchymal transition (EMT); although much is known about the role of EMT in cellular metastasis in an oncogene-transformed cell, less is known about Type II EMT, that occurring in normal epithelial cells. In this study, we applied next generation sequencing (RNA-seq) in primary human airway epithelial cells to understand the gene program controlling Type II EMT and how cytokine-induced inflammation modifies it. Generalized linear modeling was performed on a two-factor RNA-seq experiment of 6 treatments of telomerase immortalized human small airway epithelial cells (3 replicates). Using a stringent cut-off, we identified 3,478 differentially expressed genes (DEGs) in response to EMT. Unbiased transcription factor enrichment analysis identified three clusters of EMT regulators, one including SMADs/TP63 and another NF-kB/RelA. Surprisingly, we also observed 527 of the EMT DEGs were also regulated by the TNF-NF-kB/RelA pathway. This Type II EMT program was compared to Type III EMT in TGFb stimulated A549 alveolar lung cancer cells, revealing significant functional differences. Moreover, we observe that Type II EMT modifies the outcome of the TNF program, reducing IFN signaling and enhancing integrin signaling. We confirmed experimentally that TGFb-induced the NF-kB/RelA pathway by observing a 2-fold change in NF-kB/RelA nuclear translocation. A small molecule IKK inhibitor blocked TGFb-induced core transcription factor (SNAIL1, ZEB1 and Twist1) and mesenchymal gene (FN1 and VIM) expression. These data indicate that NF-kB/RelA controls a SMAD-independent gene network whose regulation is required for initiation of Type II EMT. Type II EMT dramatically affects the induction and kinetics of TNF-dependent gene networks. Overall design: A human small airway epithelial cell line was treated with TGF-Beta to induce the epithelial to mesenchymal transition. TGF-Beta treated and untreated cells were further treated with TNF-alpha for 1 and 12 hours. Three replicates for each treatment and untreated controls were performed for a total of 18 samples.
Publication Title
Analysis of the TGFβ-induced program in primary airway epithelial cells shows essential role of NF-κB/RelA signaling network in type II epithelial mesenchymal transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
transcriptome profiling of miR-92a inhibitor treated and control cells with the aim of measuring miR-92a influence on its mRNA targets
Publication Title
Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
To assay the effect of depletion of the RNA exosome on RNAs shorter than the standard length captured by RNA-seq (>200 nt), we created RNA-seq libraries using fragmented RNA and a linker-ligation-based protocol that does not deplete RNAs shorter than 200 nt. Note: these data relate to Figure 6E in Lubas, Andersen et al., Cell Reports 2014 (accepted) Overall design: These samples constitute RNA-seq libraries prepared to enrich for short RNA fragments such as snRNA and snoRNAs. Three different HeLa cell RNAi experiments were used to generate the RNA samples applied in the library construction: control transfected, hRRP40-depleted and triple-depleted of the known RNA exosome-associated ribonucleases (DIS3, DIS3L and hRRP6 knock-down). By these means the data offers reveal RNA exosome substrates via their up-regulation in the respective knock-downs NOTE: The ''Figure6E_RNAseq_DataTable_PlottedValues.txt'' was generated from total 5 samples, with two additional published samples [SRP031620] and provided to better allow readers to fully replicate the analyses presented in the publication.
Publication Title
The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 35 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 31 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 25 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 26 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 28 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana.
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 23 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
AtGenExpress: A multinational coordinated effort to uncover the transcriptome of the multicellular model organism Arabidopsis thaliana
Publication Title
The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses.
Sample Metadata Fields
Specimen part
View Samples