Transcriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The Assay for Transposase Accessible Chromatin (ATAC)-seq, coupled with transcription-factor motif analysis, provides indirect evidence of chromatin binding for hundreds of TFs genome-wide. Here, we propose methods for TRN inference in a mammalian setting, using ATAC-seq data to influence gene expression modeling. We rigorously test our methods in the context of T Helper Cell Type 17 (Th17) differentiation, generating new ATAC-seq data to complement existing Th17 genomic resources (plentiful gene expression data, TF knock-outs and ChIP-seq experiments). In this resource-rich mammalian setting our extensive benchmarking provides quantitative, genome-scale evaluation of TRN inference combining ATAC-seq and RNA-seq data. We refine and extend our previous Th17 TRN, using our new TRN inference methods to integrate all Th17 data (gene expression, ATAC-seq, TF KO, ChIP-seq). We highlight new roles for individual TFs and groups of TFs (“TF-TF modules”) in Th17 gene regulation. Given the popularity of ATAC-seq (a widely adapted protocol with high resolution and low sample input requirements), we anticipate that application of our methods will improve TRN inference in new mammalian systems and be of particular use for rare, uncharacterized cell types. Overall design: Gene expression (RNA-seq) of naive and Th17- and Th0-polarized CD4 T Cells
Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.
Specimen part, Cell line, Subject
View SamplesPurpose: The goals of this study are to compare in vitro polarized T helper 17 cell transcriptome profiling (RNA-seq) in the presence or absence of recombinant murine SAA1 Methods: Th17 mRNA profiles of 96hrs in vitro cultured T helper 17 cells treated with vehicle or recombinant murine SAA1 were generated by deep sequencing, using Illumina RapidRun. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) and TopHat followed by CuffDiff. qRT–PCR validation was performed using SYBR Green assays. Results: 177 genes were changed more than 2 folds in the presence of recombinant murine SAA1. Conclusions: Our study suggest that SAA1 could augment subset of Th17 transcription program in vitro. Overall design: mRNA profiles of 48hr in vitro cultured Th17 from wild type (WT) mice were generated by deep sequencing using Illumina RapidRun.
An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses.
No sample metadata fields
View SamplesPurpose: The goals of this study are to compare mRNAs expressed by Th17 cells and ILC3s in small intestine of lamina propria of mice. Methods: Small intestine were digested with collagenase, dispase, and DNase. Percoll enriched lamina propria Th17 and ILCs sorted by BD ARIA II. Total RNA were harvested and sequencing were performe. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) and TopHat followed by CuffDiff. qRT–PCR validation was performed using SYBR Green assays. Results: Small intestine Th17 cells and ILCs exhibit differential gene expression profiles. Overall design: compare mRNAs expressed by Th17 cells and ILC3s in small intestine of lamina propria of mice.
An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Specimen part, Treatment, Time
View SamplesType 1 regulatory T (Tr1) cells are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. Here, we show that the transcription factors IRF1 and BATF are induced early during treatment with IL-27 and are required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses reveal that both transcription factors influence chromatin accessibility and expression of genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely alter the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation. Overall design: Transcriptinal analysis of IL27-induced of WT, Irf1 KO, and Batf KO cells
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Specimen part, Cell line, Subject
View SamplesType 1 regulatory T (Tr1) cells are induced by the interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. Here, we show that the transcription factors IRF1 and BATF are induced early during treatment with IL-27 and are required for the differentiation and function of Tr1 cells in vitro and in vivo . Epigenetic and transcriptional analyses reveal that both transcription factors influence chromatin accessibility and expression of genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely alter the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation.
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Specimen part, Treatment
View Samplesretinal ganglion cells die after optic nerve injury, either crush or transection. The molecular causesunderlying this degeneration are largely unkwon
Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush.
No sample metadata fields
View SamplesThe experiment describes the transcriptional response of Saccharomyces cerevisiae BY4741 and of the deletion mutant Δhaa1 following an incubation in the presence of 50 mM acetic acid (at pH 4.0)
Genomic expression program involving the Haa1p-regulon in Saccharomyces cerevisiae response to acetic acid.
Compound
View SamplesTo try to identify the mechanism of STAT3s indirect action we have used a genomic approach to map the binding sites of STAT3 within the genome and also used RNA-seq technology to map the changes in RNA expression and transcript isoform abundance in response to IL-10. Overall design: Examination of transcriptome changes in peritoneal macrophages when treated with IL-10 for 4 hours. RNA was extracted and sequenced.
Genome-wide analysis of STAT3 binding in vivo predicts effectors of the anti-inflammatory response in macrophages.
Sex, Specimen part, Cell line, Subject
View SamplesRNA-seq was used to look at the transcriptome changes and the early events of T cell receptor stimulation in CD4+ T cells Overall design: CD4+ T cells were stimulated with immobilised anti-CD3/CD28 antibodies for 4 hours and RNA was extracted and subjected to RNA-seq analysis.
Discovery and characterization of new transcripts from RNA-seq data in mouse CD4(+) T cells.
Sex, Specimen part, Cell line, Treatment, Subject
View Samples