In order to gain insights into how PPARg regulates different facets of dendritic cell (DC) differentiation, we sought to identify PPARg regulated genes and gene networks in monocyte-derived dendritic cells using global gene expression profiling. We employed an exogenous ligand activation approach using a selective PPARg ligand (rosiglitazone abbreviated as RSG). In addition, we have defined culture conditions in which human serum (HS) induces PPARg activation via a yet uncharacterized endogenous mechanism. We also compared the gene expression profile of developing dendritic cells obtained from patients harboring dominant negative mutations of the PPARg receptor (C114R and C131Y).
PPARgamma regulates the function of human dendritic cells primarily by altering lipid metabolism.
Sex, Specimen part
View SamplesHuman monocyte derived dendritic cells matured via galectin-1 or LPS.
Galectin-1-matured human monocyte-derived dendritic cells have enhanced migration through extracellular matrix.
No sample metadata fields
View SamplesIn human breast cancers, a phenotypically distinct minority population of tumorigenic cancer (TG) cells (sometimes referred to as cancer stem cells) drives tumor growth when transplanted into immunodeficient mice. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to studying human breast cancer. To do so, we utilized breast tumors of the MMTVWnt-1 mice. MMTV-Wnt-1 breast tumors were harvested, dissociated into single cell suspensions, and FACS sorted on Thy1, CD24, and CD45. FACS sorted cells were then injected into recipient background FBV/NJ female mice. Thy1+CD24+ cancer cells, which constitute approximately 1-4% of tumor cells were highly enriched for cells capable of regenerating new tumors when compared to cells of the tumor that did not fit this profile (Not Thy1+CD24+). Resultant tumors were of the same phenotypic diversity as the original tumor and behaved in a similar manner when passaged. Microarray analysis comparing Thy1+CD24+ tumor cells to Not Thy1+CD24+ cells identified a list of differentially expressed genes. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells.
Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors.
No sample metadata fields
View SamplesBreast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells. METHODS: We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene invasiveness gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer. RESULTS: There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response (WR) signature. CONCLUSIONS: The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer.
The prognostic role of a gene signature from tumorigenic breast-cancer cells.
No sample metadata fields
View SamplesImmune cell-specific expression is one indication of the importance of a gene's role in the immune response.
Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data.
Specimen part
View SamplesRSPO is a WNT pathway activator and functions as a potent regulator of stem cell growth in colon. RSPO family members were produced by several human tumors representing multiple tumor types including ovarian, pancreatic, colon, breast and lung cancer. Specific monoclonal antibody antagonists of RSPO family members were developed. In human patient-derived tumor xenograft models, anti-RSPO treatment markedly inhibited tumor growth either as single agents or in combination with chemotherapy. Furthermore, blockade of RSPO signaling reduced the tumorigenicity of cancer cells based on serial transplantation studies.
Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates β-Catenin Signaling and Tumorigenesis in Multiple Cancer Types.
Specimen part
View SamplesBackgropund:In a major paradigm shift in the last decade, the knowledge about a whole class of non-coding RNAs known as miRNAs has emerged, which have proved these to be important regulators of a wide range of cellular processes by the way of modulation of gene expression. It is reported that some of these miRNAs are modified by addition or deletion of nucleotides at their ends, after biogenesis. However, the biogenesis and functions of these modifications are not well studied in eukaryotes, especially in plants. In this study, we examined the miRNA modifications in different tissues of the various plants, namely rice, tomato and Arabidopsis and identified some common features of such modifications. Results:We have analyzed different aspects of miRNA modifications in plants. To achieve this end, we developed a PERL script to find the modifications in the sequences using small RNA deep sequencing data. The modification occurs in both mature and passenger (star) strands, as well as at both the 5'' and 3'' ends of miRNAs. Interestingly, we found a position-specific nucleotide biased modification, as evident by increased number of modification at the 5'' end with the presence of Cytosine (nucleotide ''C'') at the 3’end of the miRNA sequence. The level of modifications is not strictly dependent on the abundance of miRNA. Our study showed that the modification events are independent of plant species, tissue and physiological conditions. Our analysis also indicates that the RNAi enzyme, namely, the RNA dependent RNA polymerase 6 (RDR6) may not have any role in Arabidopsis miRNA modifications. Some of these modified miRNAs are bound to AGO1, suggesting their possible roles in biological processes. Conclusions:This is a first report that reveals that 5'' nucleotide additions are preferred for mature miRNA sequences with 3’ terminal ‘C’ nucleotide. Our analysis also indicates that the miRNAs modifications involving addition of nucleotides to the 5’ or 3’ end are independent of RDR6 activity and are not restricted by plant species, physiological conditions and tissue types. The results also indicate that such modifications might be important for biological processes. Overall design: small RNA profiles of wild type and RDR6 (-) of Arabidopsis plants were generated using deep sequencing data.
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Subject
View SamplesHuman mucosal surfaces contain a wide range of microorganisms. The biological effects of these organisms are largely unknown. Large-scale metagenomic sequencing is emerging as a method to identify novel microbes. Unexpectedly, we identified DNA sequences homologous to virus ATCV-1, an algal virus not previously known to infect humans, in oropharyngeal samples obtained from healthy adults. The presence of ATCV-1 was associated with a modest but measurable decrease in cognitive functioning. A relationship between ATCV-1 and cognitive functioning was confirmed in a mouse model, which also indicated that exposure to ATCV-1 resulted in changes in gene expression within the brain. Our study indicates that viruses in the environment not thought to infect humans can have biological effects.
Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.
Treatment
View SamplesRNA sequencing was performed to determine the uniqueness of splenic follicular IgD low B cells compared to splenic follicular IgD high and marginal zone B cells. Overall design: Splenic follicular IgD low and IgD high , and MZ B cells were sorted by FACS from naïve 8-10 weeks old mice. Total RNA was isolated from the sorted cells using RNAqueous® -4PCR kit and RNA sequencing was performed. Splenocytes from five mice were pooled for each sorting. Three independent sorting was performed for each B cell subset.
Mature IgD<sup>low/-</sup> B cells maintain tolerance by promoting regulatory T cell homeostasis.
Specimen part, Cell line, Subject
View SamplesHepatocellular carcinoma (HCC) is the fifth most-common cancer worldwide causing nearly 600,000 deaths esch year. Approximately 80% of HCC develops on the background of cirrhosis.It is necessary to identify novel genes involved in HCC to implement new diagnostic and treatment options. However, the molecular pathogenesis of HCC largely remains unsolved. Only a few genetic alterations, namely those affecting p53, -catenin and p16INK4a have been implicated at moderate frequencies of these cancers. Early detection of HCC with appropriate treatment can decrease tumor-related deaths
Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.
Specimen part
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