These samples are being analyzed by the Duke-UNC-Texas-EBI ENCODE consortium. Expression from these cell types will compared to three whole genome open chromatin methodologies: DNaseI hypersensitivity (DNase-seq), Formaldehyde-Assisted Isolation of Regulatory elements (FAIRE-seq), and Chromatin Immunoprecipitation (ChIP-seq) .
Heritable individual-specific and allele-specific chromatin signatures in humans.
Specimen part
View SamplesComparing the relative proportions of immune cells in tumor and adjacent normal tissue from NSCLC patients demonstrates the early changes of tumor immunity and provides insights to guide immunotherapy design. We mapped the immune ecosystem using computational deconvolution of bulk transcriptome data from the Cancer Genome Atlas (TCGA) and single cell RNA sequencing (scRNA-seq) data of dissociated tumors from early-stage non-small cell lung cancer (NSCLC) to investigate early immune landscape changes occurring during tumorigenesis. Computational deconvolution of immune infiltrates in 44 NSCLC and matching adjacent normal samples from TCGA showed heterogeneous patterns of alterations in immune cells. The scRNA-seq analyses of 11,485 cells from 4 treatment-naïve NSCLC patients comparing tumor to adjacent normal tissues showed diverse changes of immune cell compositions. Notably, CD8+ T cells and NK cells are present at low levels in adjacent normal tissues, and are further decreased within tumors. Myeloid cells exhibited marked dynamic reprogramming activities, which were delineated with differentiation paths through trajectory analysis. A common differentiation path from CD14+ monocytes to M2 macrophages was identified among the 4 cases, accompanied by up-regulated genes (e.g. ALCAM/CD166, CD59, IL13RA1, IL7R) with enriched functions (adipogenesis, lysosome), and down-regulated genes (e.g. CXCL2, IL1B, IL6R) with enriched functions (TNFa signaling via NF-kB, inflammatory response). Computational deconvolution and single cell sequencing analyses have revealed a highly dynamic immune reprogramming that occurs in early stage NSCLC development, suggesting that normalizing both immune compartments may represent a viable strategy for treatment of early stage cancer and prevention of progression. Overall design: Map the immune ecosystem using computational deconvolution of bulk transcriptome data from the Cancer Genome Atlas (TCGA) and single cell RNA sequencing (scRNA-seq) data of dissociated tumors from from early-stage non-small cell lung cancer (NSCLC) to investigate early immune landscape changes occurring during tumorigenesis
Dissecting intratumoral myeloid cell plasticity by single cell RNA-seq.
Sex, Specimen part, Disease, Race, Subject
View SamplesTo examine the role of Rb1 in gastrointestinal (GI) tumors we generated mice with an Apc1638N allele, Rbtm2brn floxed alleles, and a villlin-cre transgene (RBVCA). These mice had reduced median survival due to an increase in tumor incidence and multiplicity in the cecum and the proximal colon; they differed from murine intestinal tumors of the Apc1638N type which normally arise solely in the small intestine. We have examined by micro-array analysis three cecal tumors from these mice (probable adenomas), and compared them to three duodenal tumors (probable adenocarcinomas). Expression profiles of duodenal and cecal tumors relative to each other show unique gene subsets up and down regulated. The two tumor types were subsequently shown to differentially regulate distinct sets of genes over expressed in a majority of human colorectal carcinomas.
Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the cecum and proximal colon.
No sample metadata fields
View SamplesInduced and activated regulatory CD4+ Foxp3+ cells compared
Connexin 43 signaling enhances the generation of Foxp3+ regulatory T cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesTranscriptomic comparison of 5 cell types during lethal and non-lethal influenza infection and further use of these signatures in a top-down systems analysis investigating the relative pathogenic contributions of direct viral damage to lung epithelium vs. dysregulated immunity during lethal influenza infection.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesMany components of Wnt/-catenin signaling pathway also play critical roles in mammary tumor development. To study the role of Apc in mammary tumorigensis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-Cre (progenitor) and WAP-cre (lactaing luminal) transgenic mice. Only the K14-cre mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological and molecular heterogeneity, suggesting the progenitor cell origin of these tumors. These tumors harbored truncation mutation in a very defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of -catenin signaling. Our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of -catenin signaling optimal for mammary tumor development.
Genetic mechanisms in Apc-mediated mammary tumorigenesis.
No sample metadata fields
View SamplesRecently, we identified a population of Oct4+Sca-1+Lin-CD45- very small embryonic-like stem-cells (VSELs) in adult tissues. Open chromatin structure of pluripotency genes and genomic imprinting-related epigenetic mechanisms maintain pluripotency and quiescence of VSELs, respectively. However, global transcriptome signature of this rare stem-cell population remains elusive. Here, we demonstrate by genomewide gene-expression analysis with a small number of highly purified murine bone-marrow (BM)-derived VSELs, that Oct4+ VSELs i) express a similar, yet nonidentical, transcriptome as embryonic stem-cells (ESCs), ii) up-regulate cell-cycle checkpoint genes, iii) down-regulate genes involved in protein turnover and mitogenic pathways, and iv) highly express Ezh2, a polycomb group protein.
Global gene expression analysis of very small embryonic-like stem cells reveals that the Ezh2-dependent bivalent domain mechanism contributes to their pluripotent state.
Age, Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of genistein supplementation on genome‑wide DNA methylation and gene expression in patients with localized prostate cancer.
Sex, Age
View SamplesTo identify molecular effects of genistein on mRNA levels in prostate cancer, we compared gene expression profiles of genistein-treated tumors with placebo-treated samples. There were 628 probes that reached nominally significant p-values. The genes that were differentially expressed between genistein and placebo samples were involved in angiogenesis, apoptosis, epithelial to mesenchymal transition, and tumor progression. Gene enrichment analysis suggested that PTEN and PDGF were activated, while MYC, beta-estradiol, glucocorticoid receptor NR3C1, and interferon-gamma were repressed in response to genistein treatment. These findings highlight the effects of genistein on global changes in gene expression in prostate cancer and its effects on molecular pathways involved in prostate tumorigenesis.
Effects of genistein supplementation on genome‑wide DNA methylation and gene expression in patients with localized prostate cancer.
Sex, Age
View Samples