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SRP094007
Homo sapiens
15 Downloadable Samples
Illumina HiSeq 2500
Description
Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we have compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Among these CD4+ T cell subsets, we detected differential expression of 421 proteins and 640 mRNAs, with only 48 molecules shared. Fifty proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFkB-, PI3 kinase/mTOR-, NFAT- and STAT pathways and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFkB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, while transitional FOXP3+ cells can. Our collective data reveal that Tregs protect their identity by a unique “wiring” of signalling pathways Overall design: mRNA profiles of 5 CD4+ T cell populations were generated by deep sequencing, in triplicate
Publication Title
Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 58 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
Publication Title
Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic Lymphocytic Leukemia (CLL) cells multiply in secondary lymphoid tissue but the mechanisms leading to their proliferation are still uncertain. In addition to BCR-triggered signals, other microenvironmental factors might well be involved. In proliferation centres, leukemic B cells are in close contact with CD4+CD40L+T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an IL-21-induced gene signature in CLL, containing components of JAK-STAT and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 productionex vivoby LN CD4+CXCR5+ follicular helper T cells. These results indicate that, in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL.
Publication Title
IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Bos taurus
- 12 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Our overall objective is to identify key differences in gene expression signaling pathways in the epithelial and intralobular stromal compartments during prepartum mammary remodeling and development in the dry cow.
Publication Title
Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
A specialized population of memory CD8+ T-cells resides in the epithelium of the respiratory tract to maintain protection against recurring infections. These cells express CD69 and the integrin 7 (CD103) and correspond to tissue resident memory T-cells (TRM) also described in intestine, liver and brain. A less well characterized population of CD103- CD8+ T-cells also resides in lungs and expresses markers characteristic of effector memory T-cells (TEM). We determined the transcriptional profiles of these memory CD8+ T-cell subsets retrieved from human lung resection samples and compared these with corresponding T-cell populations from peripheral blood of the same individuals. Our results demonstrate that each of the populations exhibits a distinct transcriptional identity. We found that the lung environment has a major impact on gene expression profiles. Thus, transcriptomes from CD103+ and CD103- subsets from lungs are much more resemblant to one another than to those from CD103+ or CD103- memory CD8+ T-cells from blood. TRM express specific sets of chemokine receptors, in accordance with their unique migratory properties. Furthermore, these cells constitutively express cytokine and cytotoxic genes for immediate effector function and chemokines to attract auxiliary immune cells. At the same time, multiple genes encoding inhibitory regulators are also expressed. This suggests that rapid ability to unleash effector functions is counterbalanced by programmed restraint, a combination that may be critical in the exposed but delicate tissue of the lung. Comprehensive sets of transcription factors were identified that characterize the memory CD8+ populations in the lungs. Prominent among these were components of the Notch pathway. Using mice genetically lacking expression of the NOTCH1 and NOTCH2 receptors in T-cells, we demonstrated that Notch controls both the number of lung TRM as well as the function of lung TEM. Our data illustrate the adaptation of lung resident T-cells to the requirements of the respiratory epithelial environment. Defining the molecular imprinting of these cells is important for rational vaccine design and may help to improve the properties of T-cells for adoptive cellular therapy.
Publication Title
Programs for the persistence, vigilance and control of human CD8<sup>+</sup> lung-resident memory T cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
RNA from two murine mesothelioma cell lines (AC29 and AB1) was extracted and hybridized to Affymetrix Microarrays to compare gene expression. Both mesothelioma cell lines were established following intraperitoneal introduction of crocidolite (asbestos) fibers (Davis et al. 1992) in CBA mice (AC29 cell line), and BALB/c mice (AB1).
Publication Title
Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 38 Downloadable Samples
- IlluminaHiSeq2500
Description
Tissue-resident memory T cells (Trm) are non-circulating memory T cells that localize to portals of pathogen entry such as the skin, gut and lung where they provide efficient early protection against reinfection. Trm are characterized by a molecular profile that actively prevents egress from peripheral sites including the constitutive expression of the lectin CD69 and down-regulation of the chemokine receptor (CCR)7 and sphingosine-1-phosphate receptor 1 (S1PR1). This program is partially mediated by down-regulation of the transcription factor KLF2; however, to date no transcriptional regulator specific to Trm has been identified. Here we show that the Blimp1 related transcription factor Hobit is specifically upregulated in Trm and together with Blimp1, mediates the development and maintenance of Trm in various tissues including skin, gut, liver and kidney. Importantly, we found that the Hobit/Blimp1 transcriptional module is also required for other tissue-resident lymphocytes including Natural Killer T (NKT) cells and liver tissue-resident NK cells (trNK). We show that these populations share a universal transcriptional program with Trm instructed by Hobit and Blimp1 that includes the repression of CCR7, S1PR1 and KLF2 thereby enforcing tissue retention. Our results identify Hobit and Blimp1 as major common regulators that drive the differentiation of distinct populations of tissue-resident lymphocytes. Overall design: RNA-seq data were generated for multiple tissues in mice to investigate global expression difference between resident and circulating cells.
Publication Title
Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
IL-22 acts on epithelial cells and has been shown to induce tissue protective and wound healing responses in these cells. But it has recently been decribed that IL-22 exacerbates ileatis after infection with T. gondii.
Publication Title
Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There is growing evidence that transplantation of cadaveric human islets is an effective therapy for type 1 diabetes. However, gauging the suitability of islet samples for clinical use remains a challenge. We hypothesized that islet quality is reflected in the expression of specific genes. Therefore, gene expression in 59 human islet preparations was analyzed and correlated with diabetes reversal after transplantation in diabetic mice. Analysis yielded 262 differentially expressed probesets, which together predict islet quality with 83% accuracy. Pathway analysis revealed that failing islet preparations activated inflammatory pathways, while functional islets showed increased regeneration pathway gene expression. Gene expression associated with apoptosis and oxygen consumption showed little overlap with each other or with the 262 probeset classifier, indicating that the three tests are measuring different aspects of islet cell biology. A subset of 36 probesets surpassed the predictive accuracy of the entire set for reversal of diabetes, and was further reduced by logistic regression to sets of 14 and 5 without losing accuracy. These genes were further validated with an independent cohort of 16 samples. We believe this limited number of gene classifiers in combination with other tests may provide complementary verification of islet quality prior to their clinical use.
Publication Title
Gene expression signature predicts human islet integrity and transplant functionality in diabetic mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Gene expression profiling of B-cells from a model differentiation series: from Nave B-cells, through a proliferative plasmablast stage to long-lived antibody secreting plasma cells.
Publication Title
In vitro generation of long-lived human plasma cells.
Sample Metadata Fields
Sex, Specimen part
View Samples