Transcriptome analysis of two Ph+ acute lymphoblastic leukemia cell lines after doxycycline induced silencing of MYB.
Targeting CDK6 and BCL2 Exploits the "MYB Addiction" of Ph<sup>+</sup> Acute Lymphoblastic Leukemia.
Cell line
View SamplesAffymetrix gene expression AID-GFP-positive vs AID-GFP-negative
The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia.
No sample metadata fields
View SamplesPrecursor B-lineage acute lymphoblastic leukemia (pre-B ALL) can be subdivided into different categories based on genetic abnormalities.
Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS function.
Specimen part
View SamplesDS-ALL is a highly heterogeneous disease with predominance of an aberrant exp. of CRLF2 cooperating with mutated JAK2
Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group.
Specimen part
View SamplesRecent efforts have uncovered immense transcriptional and ontogenetic diversity among tissue-resident macrophages, each with their own transcriptional profile endowing the cell with its tissue-specific functions. However, it is currently unknown whether the origins of different macrophage populations may affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone marrow-derived macrophages (BMDM) are even present in tumors of the brain, a tissue where there is no homeostatic involvement of peripherally-derived myeloid cells. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing models to demonstrate that BMDM are indeed abundant in primary and metastatic brain tumors. Transcriptional profiling of tumor-associated BMDM and resident microglia showed that these cells acquire substantially different gene expression profiles. Our data suggest that transcriptional networks in each cell population are associated with tumor-mediated education, yet are also influenced by chromatin landscapes established before tumor initiation. Furthermore, we demonstrate that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between brain-resident microglia and peripherally-derived macrophages in both primary and metastatic disease in mouse and human. Overall design: Tumor associated microglia and macrophages were isolated from mouse glioma tumors. Samples are provided as matched microglia and macrophages from 3 tumors.
Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies.
Specimen part, Cell line, Subject
View SamplesTumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis
Coordinated epidermal growth factor receptor pathway gene overexpression predicts epidermal growth factor receptor inhibitor sensitivity in pancreatic cancer.
No sample metadata fields
View SamplesMicroRNAs have been implicated in the molecular pathogenesis of calcineurin inhibitor nephrotoxicity. However, identification of bona fide physiologically relevent miRNA/mRNA targeting interactions remains a challenge. To define a comprehensive miRNA/mRNA targetome and determine the role of miRNAs in cyclsporine-induced nephrotoxicity, we performed PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) against endogenous Argonaute 2 (AGO2) protein in human proximal tubule cells treated with cyclosporine A (CsA) or vehicle control. Statistically significant mRNA targets of miRNAs in the RNA Inducing Silencing Complex (RISC) complex were identified by PIPE-CLIP, a bioinformatic framework based on a zero-truncated negative binomial model. Further, we determined the total cellular differential expression of miRNAs and mRNAs by conventional deep sequencing methods. Our data indicate that CsA causes specific changes in miRNAs and mRNAs associated with the RISC complex. A relatively small fraction of the miRNAs and mRNAs identified by total cell RNA-seq were also found in the RISC complex suggesting that changes in targeting by miRs are not necessarily reflected in changes observed in total cellular RNA. Pathway enrichment analysis after integrating miRNA-seq, mRNA-seq, and PAR-CLIP datasets identified canonical pathways specifically under regulation by miRNAs following CsA treatment. Our analysis indicates that miRNAs play an integral role in regulating widespread dysregulation of the proximal tubule cell gene program, contributing to alterations in cell-cell adhesion, integrin-cytoskeleton signaling, and calcium signaling. Analysis of high confidence 3''UTR targets revealed a specific role for miR-101-3p in regulating MAPK signaling which may contribute to the pathogenesis of cyclosporine-induced nephrotoxicity in a calcineurin-independent manner. Overall design: AGO2-PAR-CLIP, mRNA-seq, and miRNA-seq of a human kidney proximal tubule cell line (HK-2) treated with cyclosporine A or vehicle control was performed and sequenced by Illumina HiSeq 2500. Two replicate AGO2-PAR-CLIP samples in each condition and four replicates in each condition for mRNA-seq and miRNA-seq were obtained.
Defining a microRNA-mRNA interaction map for calcineurin inhibitor induced nephrotoxicity.
No sample metadata fields
View SamplesIn order to identify the effects of the induction of the gene of interest on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the different inducible cell lines
Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.
Cell line
View SamplesIn order to identify the effects of the induction of the gene of interest on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the inducible not-tagged cell line.
Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.
Cell line
View Samples