RNA editing is a mutational mechanism that specifically alters the nucleotide content in sets of transcripts while leaving their cognate genomic blueprint intact. Editing has been detected from bulk RNA-seq data in thousands of distinct transcripts, but apparent editing rates can vary widely (from under 1% to almost 100%). These observed editing rates could result from approximately equal rates of editing within each individual cell in the bulk sample, or alternatively, editing estimates from a population of cells could reflect an average of distinct, biologically significant editing signatures that vary substantially between individual cells in the population. To distinguish between these two possibilities we have constructed a hierarchical Bayesian model which quantifies the variance of editing rates at specific sites using RNA-seq data from both single cells and a cognate bulk sample consisting of ~ 106 cells. The model was applied to data from murine bone-marrow derived macrophages and dendritic cells, and predicted high variance for specific edited sites in both cell types tested. We then 1 validated these predictions using targeted amplification of specific editable transcripts from individual macrophages. Our data demonstrate substantial variance in editing signatures between single cells, supporting the notion that RNA editing generates diversity within cellular populations. Such editing-mediated RNA-level sequence diversity could contribute to the functional heterogeneity apparent in cells of the innate immune system. Overall design: 26 samples were subjected to RNA-seq: 24 single WT macrophages, and 2 bulk samples (Apobec1 WT and KO macrophages), consisting of 500,000-1 million cells each.
RNA editing generates cellular subsets with diverse sequence within populations.
Specimen part, Cell line, Subject
View SamplesAssessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress.
Deficiency in the α1 subunit of Na+/K+-ATPase enhances the anti-proliferative effect of high osmolality in nucleus pulposus intervertebral disc cells.
Specimen part
View SamplesThe metabolic syndrome (MetS) is characterized by the presence of metabolic abnormalities that include abdominal obesity, dyslipidemia, hypertension, increased blood glucose/insulin resistance, hypertriglyceridemia and increased risk for cardiovascular disease (CVD). The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model manifests several features of the MetS upon high fat diet (HFD) feeding. Moreover, the physiological changes in the white adipose tissue (WAT) contribute to MetS comorbidities. The aim of this study was to identify transcriptomic signatures in the gonadal WAT of ApoE3L.CETP mice in discrete stages of diet-induced MetS.
Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress.
Specimen part
View SamplesCD138+ B220- plasma cells were sorted from bone marrow and B220+ CD23+ mature follicular B cells were sorted from the spleens. Plasma cells were sorted from C57BL/6 mice 7 days after boosting with antigen, with mice first primed with an i.p. injection of KLH/IFA followed by boost at day 21 with KLH/PBS i.p. Mature B cells were sorted from antigen-nave C57BL/6 mice.
Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells.
Specimen part
View SamplesWe analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells.
Immunoregulatory natural killer cells suppress autoimmunity by down-regulating antigen-specific CD8+ T cells in mice.
Specimen part, Treatment
View SamplesWe have ablated TAF10 in the erythroid compartment only by crossing the TAF10lox mice with the EpoR-Cre mice and we have studied the development of the erythroid cells in vivo. TAF10 ablation led to embryonic death at E13.5 while at E12.5 there was a clear developmental defect which was reflected in the transcriptional profile of the fetal liver cells. Gata1-target genes were mostly affected and were responsible for the lethal phenotype. Overall design: mRNA from E12.5 fetal livers of TAF10lox/KO:EpoR-Cre+/- (TAF10KO) mice, TAF10HET and WT mice was profiled by NGS (Illumina).
TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis.
No sample metadata fields
View SamplesWe generated de novo induced pluripotent stem cells (iPSCs) from two Parkinson’s Disease patients (PD) harboring the p.A53T mutation. iPSC-derived mutant neurons displayed disease-relevant phenotypes at basal conditions, including protein aggregation, compromised neuritic outgrowth and contorted axons with swollen varicosities containing aSyn and tau. We have performed RNA Sequencing (RNA-Seq) of neurons from PD patient and control samples. RNA sequencing has also been performed to neurons derived from HUES samples subjected to the same differentiation protocol as reference. Overall design: We have performed RNA Sequencing (RNA-Seq) in neurons PD and control samples (two clones from each individual), along with HUES-derived neurons.
Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson's disease.
Specimen part, Subject
View SamplesPatient derived xenografts (PDX) were created from two triple-negative breast cancers (PDX-110 and PDX-332) taken at the time of surgery from drug-naive patients. Freshly sorted epithelial cells were profiled by single-cell RNA-seq (scRNA-seq) using a 10X Genomics Chromium System. Overall design: Transcriptional profiling was completed for 10,060 total epithelial cells from PDX-110 and 14,681 total epithelial cells from PDX-322.
Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer.
Specimen part, Subject
View SamplesAge-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer’s disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia. Overall design: Role of Fmn2 gene for PTSD like phenotypes and impairments of synaptic plasticity.
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.
Age, Cell line, Subject
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