Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. Overall design: Examination of how the transcriptome of normal and prostate cancer cells is altered by treatment with sulforaphane
Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.
Specimen part, Subject, Time
View SamplesThere still is a lack of specific, early markers for acute pancreatitis.
RCAN1 is a marker of oxidative stress, induced in acute pancreatitis.
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View SamplesAutoimmune pancreatitis (AIP) is a recently identified disease of the pancreas with unknown etiology and antigens. The aim of this study was to determine new target antigens and differentially regulated genes and proteins by means of transcriptomics and proteomics and to validate them in patients with autoimmune pancreatitis. Here we report a distinct downregulation at the RNA and protein level of pancreatic proteases (anionic trypsinogen, cationic trypsinogen, mesotrypsinogen, elastase IIIB) and pancreatic stone protein in autoimmune pancreatitis in comparison to alcohol-induced chronic pancreatitis.
Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process.
Sex, Age, Specimen part, Disease
View SamplesCD4+ T lymphocytes are key to immunological memory, but little is known about the lifestyle of memory CD4+ T lymphocytes. We showed that in the memory phase of specific immune responses to antigens, most of the memory CD4+ T lymphocytes relocated into the bone marrow (BM) within 3-8 weeks after their generation, a process involving integrin a2. Antigen-specific memory CD4+ T lymphocytes expressed Ly-6C to a high degree, unlike most splenic CD44hiCD62L- CD4+ T lymphocytes. In adult mice, more than 80% of Ly-6Chi CD44hiCD62L- memory CD4+ T lymphocytes were in the BM. In the BM, they are located next to IL-7-expressing VCAM-1+ stroma cells, and were in a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and induced the production of high-affinity antibodies, indicating their functional activity in vivo and marking them as professional memory T helper cells
Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.
Specimen part
View SamplesWe compared gene expression profiles of Th cells, macrophages and monocytes isolated from the inflamed colon of colitis induced by the transfer of WT versus Tbx21-/- Th cells in Rag1-/- recipients.
T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis.
Specimen part
View SamplesPathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill-defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8+ T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a MyD88-dependent, CTL-intrinsic fashion, determined polyfunctional effector cell differentiation and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses.
The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.
Specimen part
View SamplesBone marrow (BM) stromal cells are important in the development and maintenance of cells of the immune system. Using single cell RNA sequencing, we here explore the functional and phenotypic heterogeneity of individual transcriptomes of 1,167 murine BM mesenchymal stromal cells. These cells exhibit a tremendous heterogeneity of gene expression, which precludes the identification of defined subpopulations. However, according to the expression of 108 genes involved in the communication of stromal cells with hematopoietic cells, we have identified 14 non-overlapping subpopulations, with distinct cytokine or chemokine gene expression signatures. With respect to the maintenance of subsets of immune memory cells by stromal cells, we identify distinct subpopulations expressing IL7, IL15 and Tnfsf13b. Together, this study provides a comprehensive dissection of the BM stromal heterogeneity at the single cell transcriptome level and provides a basis to understand their lifestyle and their role as organizers of niches for the long-term maintenance of immune cells. Overall design: For single cell library preparation, ex vivo FACS sorted VCAM-1+CD45-Ter119-CD31- BM cells were applied to the 10X Genomics platform using the Single Cell 3' Reagent Kit V2 (10x Genomics) following the manufacturer's instructions. Upon adapter ligation and index PCR, the quality of the obtained cDNA library was assessed by Qubit quantification, Bioanalyzer fragment analysis (HS DNA Kit, Agilent) and KAPA library quantification qPCR (Roche). The sequencing was performed on a NextSeq500 device (Illumina) using a High Output v2 Kit (150 cycles) with the recommended sequencing conditions (read1: 26nt, read2: 98nt, index1: 8 nt, index2: n.a.).
Single-cell transcriptomes of murine bone marrow stromal cells reveal niche-associated heterogeneity.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Specimen part
View SamplesIL-23 negatively regulates St2 and Gata3 expression in intestinal CD4+ T cells
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Autoregulation of Th1-mediated inflammation by twist1.
No sample metadata fields
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