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SRP191376
Mus musculus
133 Downloadable Samples
NextSeq 500
Description
The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune mediated inflammatory diseases (IMIDs). Yet, despite their key role in disease, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue driven pathologies observed in IMIDs such as inflammation and damage . Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of FAPa+ synovial cells suppressed both inflammation and bone erosions in murine models of resolving and persistent arthritis. Single cell transcriptional analysis identified two distinct fibroblast subsets: FAPa+ THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPa+ THY1- destructive fibroblasts restricted to the synovial lining. When adoptively transferred into the joint, FAPa+ THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation whereas transfer of FAPa+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell based therapies aimed at modulating inflammation and tissue damage. Overall design: Serum transfer inflammatory arthritis (STIA) was induced by intravenous injection of 100 µl of arthritogenic KRN serum into naive C57BL/6 mice. From these mice, CD45-ve live Podoplanin (PDPN)+ synovial cells from hind limb joints were sort purified at day 9 (n=3 biological replicates, each comprised of cells from the joints of three animals). Individuals subsets of CD45- PDPN+ cells were further sort puified in the following populations FAP?+ THY1- (n=10 mice); FAP?+ THY+ (n=13 mice); FAP?- THY1+ (n=7 mice) and FAP?- THY1- (n=5 mice). Small bulk RNA sequencing was performed on each of these cell populations with each sample representing a biological replicate comprising of cells isolated from the synovial joints of both hind limbs from a single mouse).
Publication Title
Distinct fibroblast subsets drive inflammation and damage in arthritis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 80 Downloadable Samples
- Illumina HiSeq 2500
Description
Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-seq offers a novel way to address this problem. In this study we evaluated transcriptomic dose responses using RNA-seq in paired FFPE and frozen (FROZ) samples from two archival studies in mice, one recent (<2 years old) and the other older (>20 years old). Experimental treatments included di(2-ethylhexyl)phthalate (DEHP) and dichloroacetic acid (DCA) for the <2 and >20 year-old studies, respectively. Total RNA was ribodepleted and sequenced using the Illumina HiSeq platform. In the recent study, FFPE samples showed high concordance in total reads (98% vs FROZ), fold-change values of differentially expressed genes (DEGs) (R2 = 0.99), highly enriched target pathways (90% overlap with FROZ), and benchmark dose estimates for preselected target genes (-2% overall vs FROZ). In contrast, RNA-seq data from older FFPE samples had lower total reads (70% vs FROZ) and poor concordance in global DEGs and pathways. Despite a 99% loss of counts, dose responses were still evident for target genes in FFPE samples and positively correlated with paired FROZ samples. These findings highlight potential variability in the quality of RNA-seq data from FFPE samples. More recent FFPE samples were highly similar to FROZ samples in sequencing quality metrics, DEG profiles, and dose-response parameters, while further methods development is needed for older or lower-quality FFPE samples. This work should help broaden the use of archival resources in both chemical safety and translational science. Overall design: Trancriptomic profiles obtained using from paired frozen (FROZ) and formalin-fixed paraffin-embedded (FFPE) liver samples collected in 2013 for the DEHP study (n=16 FROZ, n=16 FFPE, with four dose groups at 0, 1500, 3000, and 6000 ppm DEHP, n=4 per dose group) and 1994 for the DCA study (n=24 FROZ, n=24 FFPE, with four dose groups at 0, 1.0, 2.0, and 3.5 g/L DCA, n=6 per dose group) using Illumina HiSeq platform.
Publication Title
Editor's Highlight: Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded Samples.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The association between chronic inflammation and the development and progression of malignancy is exemplified in the biliary tract where persistent inflammation strongly predisposes to cholangiocarcinoma. The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth in cholangiocarcinoma by altered gene expression via autocrine mechanisms. We therefore investigated the effect of chronic exposure to IL-6 on gene expression using malignant cholangiocytes stably transfected to overexpress IL-6. Comparison of gene expression identified several genes that were altered by enforced IL-6 expression.
Publication Title
Interleukin-6 contributes to growth in cholangiocarcinoma cells by aberrant promoter methylation and gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
expression profile of conditional knock out of beta-catenin by K19-CRE at E7.5. Tested a wild type with two alleles of beta-catenin, a heterzyote with one deleted allele and the conditional null in the domain on cytokeratin 19 driven CRE expression
Publication Title
Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference in mouse embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Atrial identity is determined by a COUP-TFII regulatory network.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules.
Publication Title
Atrial identity is determined by a COUP-TFII regulatory network.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Gene expression in forebrain structures change during day and night depending on circadian and rest-activity cycles. Clock genes have been shown to be involved in the control of circadian and sleep-wake control.
Publication Title
Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2000
Description
Jak1 is a ubiquitously expressed tyrosine kinase that transduces extracellular signals from a variety of cytokines and their receptors to downstream signal transducers and activators of transcription (STATs). Since deficiency in Jak1 causes early neonatal lethality, we generated Jak1 conditional knockout mice to study the biological role of this kinase during the development of the mammary gland in adult females Overall design: Total RNA was extracted from flash-frosen mammary gland tissues of seven conditional knockout females(3 lactation, 4 second day of involution) and six wildtype control mice(3 lactating, 3 involution)
Publication Title
Janus Kinase 1 Is Essential for Inflammatory Cytokine Signaling and Mammary Gland Remodeling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Pseudomonas aeruginosa
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The anaerobic metabolism of the opportunistic pathogen Pseudomonas aeruginosa is important for growth and survival during persistent infections. The two Fnr-type transcription factors Anr and Dnr regulate different parts of the underlying network. Both are proposed to bind to a non-distinguishable DNA sequence named Anr box.
Publication Title
Anaerobic adaptation in Pseudomonas aeruginosa: definition of the Anr and Dnr regulons.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples