Glial progenitor cells (GPCs) pervade the human brain. These cells express gangliosides recognized by MAb A2B5, and some but not all can generate oligodendrocytes. Since some A2B5+ GPCs express PDGFa receptor (PDGFRa), which is critical to oligodendrocyte development, we asked if PDGFRa-directed sorting might isolate oligodendrocyte-competent progenitors. We used FACS to sort PDGFRa+ cells from the second trimester fetal human forebrain, based on expression of the PDGFRa epitope CD140a. CD140a+ cells could be maintained as mitotic progenitors that could be instructed to either oligodendrocyte or astrocyte phenotype. Transplanted CD140a+ cells robustly myelinated the hypomyelinated shiverer mouse brain. Microarray confirmed that CD140a+ cells differentially expressed PDGFRA, NG2, OLIG1/2, NKX2.2 and SOX2. Some expressed CD9, thereby defining a CD140a+/CD9+ fraction of oligodendrocyte-biased progenitors. CD140a+ cells differentially expressed genes of the PTN-PTPRZ1, wnt, notch and BMP pathways, suggesting the interaction of self-renewal and fate-restricting pathways in these cells, while identifying targets for their mobilization and instruction.
CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells.
Specimen part
View SamplesPurpose: To identify genes that are transcriptionally controlled by Notch signaling during zebrafish lateral line proneuromast formation. Methods: We isolated primordium cells from dissected tails of 36 hpf Tg((cldnB:GFP);Tg(cldnB:gal4) x Tg(UAS:nicd)) and sibling Tg((cldnB:GFP);Tg(cldnB:gal4)) embryos by FACS and performed RNASeq analysis. Results: Using an optimized data analysis workflow, we mapped about 26 million sequence reads per sample to the zebrafish genome (build danRer10) and identified 32,105 transcripts in the dissociated tails of WT and NICD zebrafish with TopHat workflow. Approximately 2% of the transcripts showed differential expression between the WT and NICD tails, with a fold change =0.5 and p value <0.01. Conclusion: RNASeq analyses revealed that Notch signaling cell-autonomously induces apical constriction and cell adhesion. Overall design: Zebrafish lateral line mRNA profiles of 36 hours wild type (WT) and NICD embryos were generated in triplicate, using HiSeq 2500 (Illumina).
Proliferation-independent regulation of organ size by Fgf/Notch signaling.
No sample metadata fields
View SamplesTo identify molecular pathophysiologic changes and novel disease mechanisms specific to myelomeningocele by analyzing AFS cfRNA in fetuses with open myelomeningocele.
Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele.
No sample metadata fields
View SamplesLangerhans-cell histiocytosis (LCH) is characterized by heterogeneous lesions containing CD207+ Langerhans cells (LCs) and lymphocytes. In this study, we isolated CD207+ cells and CD3+ T cells from LCH lesions to determine cell-specific gene expression. Compared to control epidermal CD207+ cells, the LCH CD207+ cells yielded 2113 differentially-expressed genes (FDR<0.01). Surprisingly, expression of many genes previously associated with LCH, including cell-cycle regulators, pro-inflammatory cytokines and chemokines were not significantly different from control LCs in our study. However, several novel genes whose products activate and recruit T cells to sites of inflammation, including SPP1 (osteopontin), were highly over-expressed in LCH CD207+ cells. Furthermore, several genes associated with immature myeloid dendritic cells were over-expressed in LCH CD207+ cells. Compared to the peripheral CD3+ cells from LCH patients, the LCH lesion CD3+ cells yielded only 162 differentially-regulated genes (FDR<0.01), and the expression profile of the LCH lesion CD3+ cells was consistent with an activated regulatory T cell phenotype with increased expression of FOXP3, CTLA4 as well as SPP1. Based on these results, we propose a new model of LCH pathogenesis in which lesions do not arise from epidermal Langerhans cells, but from accumulation of bone-marrow derived immature myeloid dendritic cells that recruit activated lymphocytes.
Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells.
Specimen part
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 SamplesEnterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. We report the first gene expression analysis of the human host response to experimental challenge with ETEC.
Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.
Time
View SamplesWe sequenced dorsal root ganglia mRNA from 25 BXD recombinant inbred mouse strains to determine their variation in gene expression. Overall design: Dorsal root ganglia mRNA profiles of recombinant inbred mouse strains
HTR7 Mediates Serotonergic Acute and Chronic Itch.
No sample metadata fields
View SamplesThe transcriptional responses of human hosts towards influenza viral pathogens are important for understanding virus-mediated immunopathology. Despite great advances gained through studies using model organisms, the complete temporal host transcriptional responses in a natural human system are poorly understood. In a human challenge study using live influenza (H3N2/Wisconsin) viruses, we conducted a clinically uninformed (unsupervised) factor analysis on gene expression profiles and established an ab initio molecular signature that strongly correlates to symptomatic clinical disease. This is followed by the identification of 42 biomarkers whose expression patterns best differentiate early from late phases of infection. In parallel, a clinically informed (supervised) analysis revealed over-stimulation of multiple viral sensing pathways in symptomatic hosts and linked their temporal trajectory with development of diverse clinical signs and symptoms. The resultant inflammatory cytokine profiles were shown to contribute to the pathogenesis because their significant increase preceded disease manifestation by 36 hours. In subclinical asymptomatic hosts, we discovered strong transcriptional regulation of genes involved in inflammasome activation, genes encoding virus interacting proteins, and evidence of active anti-oxidant and cell-mediated innate immune response. Taken together, our findings offer insights into influenza virus-induced pathogenesis and provide a valuable tool for disease monitoring and management in natural environments.
Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.
Specimen part
View SamplesDiagnosis of influenza A infection is currently based on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with influenza A virus infection represents a novel approach to infection diagnosis
A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
Specimen part, Subject, Time
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