Despite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling performed on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T cell-associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of 6 chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative RT-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be upregulated on human CD8+ effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8+ effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8+ effector T cells when implanted as xenografts in NOD/scid mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8+ T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of anti-tumor immunity.
Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment.
No sample metadata fields
View SamplesA non-controversial and non-invasive source of adult stem cells (ASCs), particularly hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) is human umbilical cord blood. HSCs derived from cord blood have been used for treating leukemia and other blood disorders for the last 30 years. While the presence of MSCs in cord blood is limited, umbilical cord has been found to be promising source of MSCs. However, the cord is an anatomically complex organ and potential isolation of MSCs from its various parts has not been fully explored.
Isolation and comparative analysis of potential stem/progenitor cells from different regions of human umbilical cord.
Specimen part
View SamplesThe transcriptional events accompanying synaptogenesis are largely unknown, or have been studied in systems in which synapse formation occurs gradually over time. With a system in which synaptogenesis is synchronized and controllable, molecular or biochemical techniques can be used to examine cellular events across cultures on a wide scale, as synapses develop.
Synaptogenesis in purified cortical subplate neurons.
No sample metadata fields
View SamplesTotal RNA from peripheral blood mononuclear cells (PBMC) and neutrophils from children with juvenile dermatomyositis (JDM) and juvenile idiopathic arthritis (JIA) were separately compared to pediatric control samples.
Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment.
No sample metadata fields
View SamplesCbx3 (HP1?) that is a member of the heterochromatin protein 1 family play important roles in development and differentiation. To determine the regulatroy mechanisms of Cbx3 during neural differentiation from ESCs to NPCs, we performed RNA-seq analysis of ESCs or ESC-derived NPCs depleted for Cbx3 or Cbx3-assocatied Mediator subunit Med26. Overall design: ESCs or ESC-derived NPCs were transfected with control siRNA targeting to luciferase or siRNA mediated knockdown of Cbx3 or Med26. RNAs were extracted from control or knockdown group and subjected to library preparation and deep sequencing.
Cbx3 maintains lineage specificity during neural differentiation.
Specimen part, Cell line, Subject
View SamplesTransition from a partially reprogrammed pre-iPSC state to iPSC state can be achieved by modulating levels of histone modifying enzymes or proteins that can bind to histone modifications
Proteomic and genomic approaches reveal critical functions of H3K9 methylation and heterochromatin protein-1γ in reprogramming to pluripotency.
Specimen part
View SamplesAbstract: During Drosophila oogenesis, germline stem cell (GSC) identity is maintained largely by preventing the expression of factors that promote differentiation. This is accomplished via the activity of several genes acting either in the GSC or its niche. The translational repressors, Nanos and Pumilio, act in GSCs to prevent differentiation, likely by inhibiting translation of early differentiation factors, while niche signals prevent differentiation by silencing transcription of the differentiation factor Bam. We have found that the DNA-associated protein Stonewall (Stwl) is also required for GSC maintenance. stwl is required cell-autonomously; clones of stwl- germ cells were lost by differentiation, and ectopic Stwl caused an expansion of GSCs. stwl mutants acted as Suppressors of Variegation, indicating stwl normally acts in chromatin-dependent gene repression. In contrast to several previously described GSC maintenance factors, Stwl likely functions epigenetically to prevent GSC differentiation. Stwl-dependent transcriptional repression does not target bam, but rather Stwl represses the expression of many genes, including those that may be targeted by Nanos/Pumilio translational inhibition.
Stonewalling Drosophila stem cell differentiation by epigenetic controls.
No sample metadata fields
View SamplesIdentify biomarkers to predict response to therapy in polyarticular juvenile idiopathic arthritis (JIA) using gene expression microarrays.
The meaning of clinical remission in polyarticular juvenile idiopathic arthritis: gene expression profiling in peripheral blood mononuclear cells identifies distinct disease states.
Specimen part, Disease, Disease stage
View SamplesThe aim of this study was to employ a systems-level analysis to elucidate gene expression networks operating in the CD4 T-cell responses which underpin human atopic disease.
A network modeling approach to analysis of the Th2 memory responses underlying human atopic disease.
Time
View SamplesWhile prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular.
Transcriptomic responses to prion disease in rats.
Specimen part, Disease
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