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Series GSE84135 Query DataSets for GSE84135
Status Public on Sep 26, 2018
Title The NFkB subunit RELA is a master transcriptional regulator of the committed epithelial-mesenchymal transition in airway epithelial cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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 β (TGFβ) 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 TGFβ-induced EMT transition was analyzed by RNA-Seq in the absence or presence of inducible shRNA-mediated silencing of RELA. In WT cells, TGFβ stimulation significantly affected the expression of 2,441 genes. Gene set enrichment analysis identified Wnt, cadherin, and NFkB signaling as the most prominent TGFβ-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/β-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 TGFβ-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
Contributor(s) Brasier AR, Widen SG
Citation(s) 30166344
Submission date Jul 07, 2016
Last update date May 22, 2019
Contact name Allan Brasier
Phone 409-772-2824
Organization name University Texas Medical Branch
Department Medicine
Street address 301 Univ. Blvd
City Galveston
State/province TX
ZIP/Postal code 77555-1060
Country USA
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (18)
GSM2227583 WTd0_A
GSM2227584 WTd0_B
GSM2227585 WTd0_C
BioProject PRJNA328132
SRA SRP078053

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Supplementary file Size Download File type/resource
GSE84135_DESeq_rld.counts.tsv.gz 3.3 Mb (ftp)(http) TSV
GSE84135_all.counts.tsv.gz 708.1 Kb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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