SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice.
Loss of IGFBP7 expression and persistent AKT activation contribute to SMARCB1/Snf5-mediated tumorigenesis.
Specimen part, Cell line
View SamplesNGS was used in order to discover novel downstream targets of the miR-17-92/106b clusters. Overall design: Comperasion of gene expression from miR-17-92/106b KO and control
miR-17-92 and miR-106b-25 clusters regulate beta cell mitotic checkpoint and insulin secretion in mice.
Specimen part, Cell line, Subject
View SamplesHow organ size and form are controlled during development is a major question of biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here we report that non-nutritional signals from blood vessels surprisingly act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
Blood vessels restrain pancreas branching, differentiation and growth.
Specimen part
View SamplesWe have developed a new transgenic mouse strain, expressing a CyclinB1-GFP fusion reporter, which marks replicating cells in the S/G2/M phases of the cell cycle to isolate live replicating and quiescent cells from the liver.
A transgenic mouse marking live replicating cells reveals in vivo transcriptional program of proliferation.
Age, Specimen part
View SamplesTranscriptome of beta-cells isolated from mice expressing p16ink4a and GFP transgenes and of control ß-cells isolated from mice expressing only the GFP transgene Overall design: RNAseq of murine beta-cells sorted based on GFP expression from three Ins-rtTA/tet-GFP/tet-p16ink4a mice and two control Ins-rtTA/tet-GFP mice following 10 days tet-mediated induction.
p16(Ink4a)-induced senescence of pancreatic beta cells enhances insulin secretion.
Specimen part, Subject
View SamplesIncreased antigen cross-presentation but impaired cross-priming after activation of PPAR is mediated by up-regulation of B7H1
Increased antigen cross-presentation but impaired cross-priming after activation of peroxisome proliferator-activated receptor gamma is mediated by up-regulation of B7H1.
Specimen part
View SamplesHeterotopic cardiac transplants were constructed in male Wistar Furth (allograft donor) and ACI (host) rats. Rats were divided into three groups consisting of no treatment, treatment with a sub-therapeutic dose of cyclosporin A, and treated with combination of a sub-therapeutic dose of cyclosporin A and allochimeric peptide. The allografts were harvested at defined periods post-transplantation and RNA was harvested to monitor gene expression changes resulting from the various treatments in T-cells and in heart cells.
Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.
Sex, Specimen part
View SamplesGenome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Cell line, Treatment, Time
View SamplesDeregulation of cytokine- and growth factor signaling due to altered expression of endogenous regulators is well recognized in prostate and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of growth hormone, IGF and prolactin signaling, that have been implicated in carcinogenesis. In this study we elucidate expression pattern and functional significance of SOCS2 in prostate cancer (PCa). Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed significantly enhanced expression in tumor compared to benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited prostate cancer cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we prove for the first time that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with androgen receptor expression in malignant tissue of patients. Taken together, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo.
SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer.
Treatment, Time
View SamplesT cells in mucosal tissues fulfill a complex array of duties to ensure maintenance of barrier immunity. In oral mucosa tissue, we found that increased inflammation altered CD4 T cell subsets in a spatially-dependent manner, although it had a modest effect on the frequency of tissue-resident memory T cells (TRM) and the CD4 T cell transcriptome. In contrast, localization to the tissue profoundly altered the transcriptional profile, emphasizing the importance of studying healthy tissue to understand disease-specific changes. Our data revealed the existence of a TH17 cell population that is predominantly found in the tissue-resident, but not transient, CD4 T cell compartment in mucosal tissue. Overall design: This project contains bulk RNA-seq data from paired oral mucosa tissue and blood CD4 T cell subsets from 10 subjects and 10X genomics sequencing of CD4 T cell subsets from one individual
The human tissue-resident CCR5<sup>+</sup> T cell compartment maintains protective and functional properties during inflammation.
Specimen part, Subject
View Samples