We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia-cell-expression levels that varied among patients. CLL cells that expressed ZAP-70 or that used unmutated IGHV each had a median expression-level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3 UTRs having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that may enhance B-cell receptor (BCR) signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 levels was a significant independent predictor of longer treatment-free-survival (TFS) or overall survival (OS), whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for OS. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor (BCR), thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.
miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1.
Specimen part, Disease stage
View SamplesCortical GABAergic interneurons constitute a highly diverse population of inhibitory neurons that are key regulators of cortical microcircuit function. An important and heterogeneous group of cortical interneurons specifically expresses the serotonin receptor 3A (5-HT3AR) but how this diversity emerges during development is poorly understood. Here we use single-cell transcriptomics to identify gene expression patterns operating in Htr3a-GFP+ interneurons during early steps of cortical circuit assembly. We identify 3 main molecular types of Htr3a-GFP+ interneurons, each displaying distinct developmental dynamics of gene expression. The transcription factor Meis2 is specifically enriched in a type of Htr3a-GFP+ interneurons spatially confined to the cortical white matter. These MEIS2 expressing interneurons appear to originate from a restricted region located at the embryonic pallial-subpallial boundary. Overall, this study identifies MEIS2 as a subclass-specific marker for 5-HT3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled. Overall design: Single cell transcriptomics of cortical interneurons FACS sorted according to GFP-Htr3a+. Acquired from mouse brains of 3 different developmental ages: E18, P2, P5
Transcriptomic and anatomic parcellation of 5-HT<sub>3A</sub>R expressing cortical interneuron subtypes revealed by single-cell RNA sequencing.
Subject
View SamplesTranscriptome sequencing of Chronic Phase and Blast Crisis CML, normal cord blood cells, and normal cord blood cells transduced with lentiviral vectors
ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.
No sample metadata fields
View SamplesGene expression was analyzed and compared of normal mouse hepatocyte, premalignant hepatocytes and fully malignant HCC cells. The results provide valuable information about the gene expression alterations during the chronic process of liver cancer development.
Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling.
Specimen part
View SamplesPurpose: The goals of this study were to identify quantitative gene expression differences between whole tumor and tumor-associated macrophages (TAMs) derived from Lewis lung carcinoma (LLC) tumors grown in wild type and PI3Kinase-gamma-null mice. Methods: mRNA profiles of whole tumor or tumor-associated macrophages (CD11b+Gr1- cells) from wild type (WT) or PI3Kinase-gamma-knockout (p110g-/-) mice were generated by single deep read sequencing, in triplicate or quadruplicate, using Illumina HiSeq 2000. The sequence reads that passed quality filters were aligned to mouse transcriptome using the bowtie2 aligner. Gene-level summaries were normalized and analyzed for differential expression using DESeq. Overall design: mRNA profiles of whole tumor and tumor-associated macrophages from WT and p110g-/- mice were generated by deep sequencing in triplicate or quadruplicate using Illumina HiSeq 2000.
PI3Kγ is a molecular switch that controls immune suppression.
Specimen part, Subject, Time
View SamplesPurpose: The goals of this study were to identify quantitative gene expression differences between macrophages derived from wild type and PI3Kgamma null macrophages Methods: mRNA profiles of MCSF, IL4 and IFNg/LPS stimulated macrophage wild-type (WT) and PI3Kinase gamma knockout (p110g-/-) mice were generated by single read deep sequencing, in triplicate, using Illumina HiSeq2000. The sequence reads that passed quality filters were aligned to mouse transcriptome using the bowtie2 aligner. Gene-level summaries were normalized and analyzed for differential expression using DESeq. qRT–PCR validation was performed using SYBR Green assays. Conclusions: Our study represents the first detailed analysis of the role of p110g in the control of the macrophage immune response, with biological replicates, generated by RNA-seq technology. Overall design: mRNA profiles of wild type (WT) and p110g-/- macrophages were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.
PI3Kγ is a molecular switch that controls immune suppression.
No sample metadata fields
View SamplesStudies of the RNA polymerase-binding molecule ppGpp in bacteria and plants have shown that changes to the kinetics of the RNA polymerase can have dramatic biological effects in the short-term as a stress response. Here we describe the reprogramming of the kinetic parameters of the RNAP through mutations arising during laboratory adaptive evolution of Escherichia coli in minimal media. The mutations cause a 10- to 30-fold decrease in open complex stability at a ribosomal promoter and approximately a 10-fold decrease in transcriptional pausing in the his operon. The kinetic changes coincide with large scale transcriptional changes, including strong downregulation of motility, acid-resistance, fimbria, and curlin genes which are observed in site-directed mutants containing the RNA polymerase mutations as well as the evolved strains harboring the mutations. Site-directed mutants also grow 60% faster than the parent strain and convert the carbon-source 15% to 35% more efficiently to biomass. The results show that long-term adjustment of the kinetic parameters of RNA polymerase through mutation can be important for adaptation to a condition.
RNA polymerase mutants found through adaptive evolution reprogram Escherichia coli for optimal growth in minimal media.
No sample metadata fields
View SamplesAnalysis of the transcriptome of mononuclear side population (SP) and main population (MP) cells of human fetal skeletal muscle from 12 human subjects of gestational age 14-18 weeks.
Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin.
Specimen part
View SamplesFunctional analysis of ABCB5 in A375 and G3361 melanoma cells, by comparing stably-transfected controls to ABCB5-shRNA-targeted cells.
ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit.
Specimen part, Cell line
View SamplesTo find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice
Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
Sex, Specimen part
View Samples