RNAseq is performed (50bp single end reads) on SW480, HT-29, HCT-15, HCT-116, COLO 205, and COLO 320 cell lines after DMSO or JQ1 treatment Overall design: Examination of transcriptomic changes after JQ1 treatment
CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer.
No sample metadata fields
View SamplesRNAseq is performed (50bp single end reads) on HT-29 and HCT-116 cell lines utilizing two independent shRNAs against BRD4 and a non-targeting control shRNA (NTC) Overall design: Examination of transcriptomic changes after knockdown of BRD4
CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer.
No sample metadata fields
View SamplesBCRABL1+ precursor B-cell acute lymphoblastic leukemia (BCR ABL1+ B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCRABL1+ B-ALL cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBP or PU.1. The resultant cells were clonally related to the primary leukemic blasts but resembled normal macrophages in appearance, immunophenotype, gene expression, and function. Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts, indicating that lineage reprogramming eliminates the leukemogenicity of BCRABL1+ B-ALL cells, and suggesting a previously unidentified therapeutic strategy for this disease. Finally, we determined that myeloid reprogramming may occur to some degree in human patients by identifying primary CD14+ monocytes/ macrophages in BCRABL1+ B-ALL patient samples that possess the BCRABL1+ translocation and clonally recombined VDJ regions.
Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages.
No sample metadata fields
View SamplesWe access the activity-dependent genes in olfactory neuron cells with unilateral naris occlusion model with mouse. Overall design: mRNA profile of olfactory epithelia between closed and open sides of mice naris was compared
Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium.
Specimen part, Cell line, Subject
View SamplesOver one million prostate biopsies are performed in the U.S. every year. However, pathology examination is not definitive in a significant percentage of cases due limited diagnostic tumor. We have observed that the microenvironment of prostate tumor cells exhibits numerous differential gene expression changes and have asked whether such information can be used to distinguish tumor from nontumor. We initially compared expression analysis data (Affymetrix U133plus2) from 18 volunteer biopsy specimens to 17 specimens containing largely tumor-adjacent stroma and identified 964 significant (p_adj < 0.01 and B > 0) expression changes. These genes were filtered to eliminate possible aging-related genes and genes expressed in tumor cells > 10% of the stroma cell expression level leading to 23 candidate genes (28 Affymetrix probe sets). A classifier based on the 28 probe sets was tested on 289 independent cases, including 195 tumor-bearing cases, 99 nontumor cases (normal biopsies, normal autopsies, remote stroma as well as pure tumor adjacent stroma) all with accuracies >85%, sensitivities >90% and specificities >85%. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for categorization as tumor and nontumor.
In silico estimates of tissue components in surgical samples based on expression profiling data.
Subject
View SamplesProstate cancer gene expression profiles were studied in this project. A total RNA from 148 prostate sample with various amount of different cell types were hybridized to Affymetrix U133A arrays. The percentage of different cell types vary considerably among samples and were determined by pathologist. Cell type specific genes can be determined by linear regression using the methods of Stuart et al, PNAS, 2004.
In silico estimates of tissue components in surgical samples based on expression profiling data.
No sample metadata fields
View SamplesTo examine the transcriptome of early testicular somatic cells during gonadogenesis at 12.5dpc RNA sequencing (RNA-Seq) was performed on murine primary testicular cell lineages isolated from the Sf1-eGFP line by FACS. The three main somatic cell lineages of the testis were isolated: the Sertoli cells which direct male development; the fetal Leydig cells (FLCs) that produce steroid hormones and virilise the XY individual and a heterogenous population of interstitial cells, some of which give rise to the adult Leydig cells (ALCs). This dataset provides a platform for exploring the biology of FLCs and understanding the role of these cells in testicular development and masculinization of the embryo, and a basis for targeted studies designed to identify causes of idiopathic XY DSD. Overall design: RNA-Seq of 3 enriched cell populations from 12.5dpc mouse gonad (Sertoli cells, Leydig cells and Interstitial cells isolated by FACS-sorting) on an Illumina HiSeq 1500, in triplicate.
Purification and Transcriptomic Analysis of Mouse Fetal Leydig Cells Reveals Candidate Genes for Specification of Gonadal Steroidogenic Cells.
No sample metadata fields
View SamplesPrevious studies have revealed that UV-stimulation of a variety of cells leads to activation of the EGF receptor, induction of Egr1, growth inhibition and apoptosis. On the other hand both Egr1 and EGF receptor activation are implicated in promoting the progression of prostate cancer. We treated M12 tumorigenic prostate epithelial cells which express little Egr1 with UV irradiation which rapidly activated the EGF receptor and elevated Egr1. Treatment with specific EGFR and ERKI/II inhibitors (PD153035 and UO126, respectively) confirmed that the upregulation of Egr1 was downstream of EGFR and ERKI/II Map kinase pathway. ChIP on chip experiments using Egr1 antibody identified 288 significantly bound promoters upon UV stimulation. Of these target genes, 40% had consensus Egr1 site in their promoters, considerably greater than that expected by chance (p < 0.005). The array binding results were validated by PCR analysis of 25 genes using DNA from conventional IP experiment. Affymetrix gene expression analysis of UV treated and control cells confirmed that a significant number of these bound promoters showed gene expression changes. Addition of siRNA to Egr1 confirmed that the gene expression changes were dependent upon Egr1 expression. Addition of EGF led to similar expression changes for nine tested genes. Proliferation and apoptosis assays confirmed that M12 cells undergo growth arrest and apoptosis following UV irradiation. Moreover, addition of EGF also promoted significant growth inhibition. These results indicate the M12 cells undergo a EGF receptor dependent apoptosis response upon UV-stimulation and that Egr1 mediates the regulation of numerous genes downstream of the EGF receptor that are associated with this response.
Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip.
No sample metadata fields
View SamplesBreast cancer is a highly heterogeneous disease that is categorized into distinct tumor subtypes based on specific molecular attributes, which ultimately influence therapeutic options. Unlike ER+ and/or HER2+ cancers that are subject to specific targeted therapies, triple negative breast cancers (TNBCs) do not express these receptors, which leaves patients with limited treatment options. Thus, significant focus has been placed on identifying molecular attributes of basal-like disease that could be used to develop and/or direct novel treatment regimens. Activation of MYC signaling and inactivation of the RB-pathway are frequent events in many types of human cancers. These pathways influence many biological processes, such as cell proliferation, that contribute to the aggressiveness and therapeutic response of tumors. The current study examines the interaction of the MYC and RB pathways in mammary epithelial cell tumorigenesis.
RB loss contributes to aggressive tumor phenotypes in MYC-driven triple negative breast cancer.
Sex, Age, Specimen part
View SamplesGenetic variation modulating risk of sporadic Parkinson's disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1 null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Overall design: 473 single cell RNA-Seq samples from sorted mouse Th-eGFP+ dopaminergic neurons collected at two timepoints from three distinct brain regions.
Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.
Specimen part, Subject
View Samples