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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- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-sequencing of SSP RNA from patients with serrated polyposis syndrome identifies VSIG1 and MUC17 as potential diagnostic markers for SSPs Overall design: 5'' capped RNA from seven ascending SSPs, six patient matched uninvolved right colon and two normal right colon samples was used for RNA sequencing (15 samples total)
Publication Title
RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers.
Sample Metadata Fields
Sex, Disease, Subject
View Samples- Bos taurus
- 10 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
In cattle, almost all fully grown vesicle stage oocytes (GV) have the ability to resume meisos, develop to Metaphase II stage (MII), support fertilization and progress through the early embryonic cycles in vitro. Yet without intensive selection, the majority fail to develop to the blastocyst stage.
Publication Title
Sequential analysis of global gene expression profiles in immature and in vitro matured bovine oocytes: potential molecular markers of oocyte maturation.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 37 Downloadable Samples
- Illumina Genome Analyzer II
Description
The estrous cycles of Limousin heifers (n = 30) were synchronized by insertion of a controlled internal drug release (CIDR) device (1.94 g progesterone; Pfizer Animal Health) placed into the vagina for 8 days. A 0.5 mg intramuscular injection of a prostaglandin F2a (PG) analogue (PG, Estrumate, Shering-Plough Animal Health, Hertfordshire, UK) was administered 1 day before CIDR removal. Heifers were checked for standing estrus and only those exhibiting estrus (Day 0) were used. All animals were expected to come in heat between 48 and 72 hours after CIDR removal. Cervical tissues were collected at slaughter from heifers 12h after CIDR removal (Group 1: CIDR + 12 h, n = 6), 24h after CIDR removal (Group 2: CIDR + 24 h, n = 6), at the onset of estrus (Group 3: Estrus, n = 4), 12 h after the onset of estrus (Group 4: estrus + 12 h, n = 5), 48 h after the onset of estrus (Group 5: Estrus+48h, n = 4) and on day 7 after the onset of estrus (Group 6: Luteal phase, n = 5). Overall design: Cervical tissue from 30 animals taken at 6 timepoints in the peri-oestrus period. +12hrs post CIDR, Onset of Oestrus,+12hrs post Oestrus, +48hrs post Oestrus, Luteal phase
Publication Title
Molecular aspects of mucin biosynthesis and mucus formation in the bovine cervix during the periestrous period.
Sample Metadata Fields
Subject, Time
View Samples- Bos taurus
- 77 Downloadable Samples
- Illumina HiSeq 2000
Description
Mycobacterium bovis, the agent of bovine tuberculosis, causes an estimated $3 billion annual losses to global agriculture due, in part, to the limitations of current diagnostics. Development of next-generation diagnostics requires a greater understanding of the interaction between the pathogen and the bovine host. Therefore, to explore the early response of the alveolar macrophage to infection, we report the first application of RNA-sequencing to define, in exquisite detail, the transcriptomes of M. bovis-infected and non-infected alveolar macrophages from ten calves at 2, 6, 24 and 48?hours post-infection. Differentially expressed sense genes were detected at these time points that revealed enrichment of innate immune signalling functions, and transcriptional suppression of host defence mechanisms (e.g., lysosome maturation). We also detected differentially expressed natural antisense transcripts, which may play a role in subverting innate immune mechanisms following infection. Furthermore, we report differential expression of novel bovine genes, some of which have immune-related functions based on orthology with human proteins. This is the first in-depth transcriptomics investigation of the alveolar macrophage response to the early stages of M. bovis infection and reveals complex patterns of gene expression and regulation that underlie the immunomodulatory mechanisms used by M. bovis to evade host defence mechanisms. Overall design: Whole-transcriptome analysis of M. bovis- and non-infected alveolar macrophages from ten calves (n = 10) at 2, 6, 24 and 48 hours (h) post-infection using RNA-sequencing (RNA-seq).
Publication Title
RNA sequencing provides exquisite insight into the manipulation of the alveolar macrophage by tubercle bacilli.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of TH17 cells redirected with chimeric antigen receptors (CAR) expressing various signaling domains (including CD28, 4-1BB and ICOS) after surrogate antigen stimulation.
Publication Title
ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Bos taurus
- 78 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
An increase in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our objective was to ascertain differential effects of elevated P4 concentrations following conception on endometrial gene expression in beef heifers on Days 5, 7, 13 and 16 of pregnancy, corresponding to the morula, blastocyst, elongation and maternal recognition of pregnancy stages, respectively. Estrus was synchronized in beef heifers (N=263). Two-thirds (N=140) were inseminated (Day 0), and all animals were randomly assigned to one of the following treatments: (i) pregnant, high P4; (ii) pregnant, normal P4; (iii) cycling, high P4; (iv) and cycling, normal P4. All high P4 groups received a P4 release intravaginal device (PRID) on Day 3 post-estrus/mating. Tissue was collected on Days 5, 7, 13 or 16 of the cycle or pregnancy, and pregnancy was confirmed by the presence of an appropriately developed embryo/conceptus. PRID insertion elevated (P<0.05) P4 concentrations from Day 3.5 to 8 compared with untreated animals and conceptus size was larger (P<0.05) in animals with elevated P4 on Days 13 and 16 compared with normal P4. Total RNA was extracted from predominantly intercaruncular endometria from the ipsilateral uterine horn. Samples from individual heifers were selected on the basis of their P4 profiles and gene expression was analyzed using bovine Affymetrix microarrays (N=5 per treatment per time point). Microarray data from analyses using Bioconductor GCRMA and Limma packages were subjected to a modified t-test and P-values were adjusted for multiple testing using the Benjamin and Hochberg false discovery rate method. Differentially expressed genes were selected on the basis of an adjusted P-value of <0.01. There were no detectable differences in gene expression in endometria from pregnant and cyclic heifers on Days 5, 7 and 13 post-estrus, but, the expression of 764 genes was altered due to the presence of the conceptus at maternal recognition of pregnancy (Day 16). On Days 5 and 7, elevated P4 in pregnant heifers, altered the expression of 36 and 124 genes respectively but on Days 13 and 16 there were relatively few DEG between high and normal P4 heifers (15 and 25). Of the genes that were differentially regulated by P4, the majority were unique to a specific day of the estrous cycle/early pregnancy. In conclusion, gene expression in endometria did not differ between pregnant and cycling heifers until Day 16 of pregnancy (i.e. the time of maternal recognition of pregnancy and production of interferon tau by conceptus trophectoderm); however, elevating P4 in early pregnancy programmed changes in gene expression in endometria that are hypothesized to impact early conceptus growth and development. Thus, on Days 5, 7 and 13 differential gene expression was affected by P4, but on Day 16 the conceptus primarily influenced gene expression in uterine endometria of heifers.
Publication Title
Conceptus-induced changes in the endometrial transcriptome: how soon does the cow know she is pregnant?
Sample Metadata Fields
Specimen part, Time
View Samples- Bos taurus
- 65 Downloadable Samples
- Illumina Genome Analyzer II
Description
Cellular mechanisms that contribute to low estradiol concentrations produced by the preovulatory ovarian follicle in cattle with a compromised metabolic status (such as lactatino) are largely unknown. To gain insight into the main metabolic mechanisms affecting preovulatory follicle function RNAseq profiling was conducted on non-lactating Holstein-Friesian heifers (n=16) and lactating Holstein-Friesian cows (n=17) at three stages of preovulatory follicle development: A) newly selected dominant follicle in the luteal phase (Selection); B) follicular phase before the LH surge (Differentiation) and C) pre-ovulatory phase after the LH surge (Luteinization). Based on a combination of RNA sequencing, ingenuity pathway analysis and Q-RT-PCR validation several important molecular markers involved in steroid biosynthesis, such as the expression of steroidogenic acute regulatory protein (STAR) within developing dominant follicles, were identified to be affected (downregulated) by the catabolic state. We propose that the adverse metabolic environment caused by lactation decreases preovulatory follicle function by affecting cholesterol transport into the mitochondria to initiate steroidogenesis. Overall design: Granulosa and Theca samples from the dominant follicle were taken from cows and heifers at stages: selection, differentiation and luteinization.
Publication Title
Effect of the metabolic environment at key stages of follicle development in cattle: focus on steroid biosynthesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this data set we include expression data from human CD4+ T cells isolated on day 0, 6, 11 and 24 follow anti-CD3/anti-CD28 magnetic bead stimulation and chimeric antigen receptor transduction.
Publication Title
Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- IlluminaHiSeq2000
Description
We recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2a phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498). Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2a and induced no major changes in translation or mRNA levels in unstressed cells. eIF2a phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2a phosphorylation, SG formation and cognitive loss. Overall design: Ribosome profiling with paired RNA-seq
Publication Title
The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly.
Sample Metadata Fields
No sample metadata fields
View Samples