We used microarrays to detail the transcriptome-wide gene expression changes underlying chemical conversion of human fibroblasts into induced Schwann Cells over a time period of 39 days. We compared then the expression profiles of these induced Schwann Cells to primary Schwann cells.
Chemical conversion of human fibroblasts into functional Schwann cells.
Specimen part
View SamplesMyogenic differentiation relies on Pax7 function. We used mouse embryonic fibroblasts lacking functional Pax7 to follow its role in terminally differentiated cells.
Cell cycle regulation of embryonic stem cells and mouse embryonic fibroblasts lacking functional Pax7.
Specimen part
View SamplesWe analyzed the transcriptome of the C57BL/6J mouse hypothalamus, hippocampus, neocortex, and cerebellum to determine estrous cycle-specific changes in these four brain regions. We found almost 16,000 genes are present in one or more of the brain areas but only 210 genes, ~1.3%, are significantly changed as a result of the estrous cycle. The hippocampus has the largest number of differentially expressed genes (DEGs) (82), followed by the neocortex (76), hypothalamus (63), and cerebellum (26). Most of these DEGs (186/210) are differentially expressed in only one of the four brain regions. A key finding is the unique expression pattern of growth hormone (Gh) and prolactin (Prl). Gh and Prl are the only DEGs to be expressed during only one stage of the estrous cycle (metestrus). To gain insight into the function of the DEGs, we examined gene ontology and phenotype enrichment and found significant enrichment for genes associated with myelination, hormone stimulus, and abnormal hormone levels. Additionally, 61 of the 210 DEGs are known to change in response to estrogen in the brain. 50 genes differentially expressed as a result of the estrous cycle are related to myelin and oligodendrocytes and 12 of the 63 DEGs in the hypothalamus are oligodendrocyte- and myelin-specific genes. This transcriptomic analysis reveals that gene expression in the female mouse brain is remarkably stable during the estrous cycle and demonstrates that the genes that do fluctuate are functionally related. Overall design: Hypothalamus, hippocampus, neocortex, and cerebellum mRNA from adult female C57BL/6J (B6) mice were analyzed by RNA sequencing of 3 biological replicates for each of the 4 stages of the estrous cycle using an Illumina HiSeq 2500
The stability of the transcriptome during the estrous cycle in four regions of the mouse brain.
Sex, Age, Specimen part, Cell line, Subject
View SamplesA variety of neurological disorders, including Alzheimer's disease, Parkinson's disease, major depressive disorder, dyslexia and autism, are differentially prevalent between females and males. To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we measured both mRNA and protein in the hippocampus of female and male mice at 1, 2, and 4 months of age with RNA-sequencing and mass-spectrometry respectively. Differential expression analyses identify 2699 genes that are differentially expressed between animals of different ages. 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation across all ages, 8 of which are heat-shock proteins. We also find a modest correlation between levels of mRNA and protein in the mouse hippocampus (Rho = 0.53). This study adds to the substantial body of evidence for transcriptomic regulation in the hippocampus during postnatal development. Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus. Overall design: Hippocampal mRNA from 1, 2, and 4 month old male and female B6 mice were analyzed by RNA sequencing of 5 biological replicates using an Illumina HiSeq 2500
Sex differences in the molecular signature of the developing mouse hippocampus.
Sex, Age, Specimen part, Cell line, Subject
View SamplesNumerous neurological disorders, including Alzheimer's disease, display a sex-biased prevalence. To identify molecular correlates of this sex bias, we investigated sex-differences in molecular pathology in the hippocampus using the 5XFAD mouse model of Alzheimer's disease during early stages of disease progression (1, 2, and 4 months of age). Overall design: Hippocampal mRNA from 1, 2, and 4 month old male and female 5XFAD mice were analyzed by RNA sequencing of 5 biological replicates using an Illumina HiSeq 2500
Sex-biased hippocampal pathology in the 5XFAD mouse model of Alzheimer's disease: A multi-omic analysis.
Sex, Age, Specimen part, Cell line, Subject
View SamplesAnalysis of gene expression over serial 150um sections of a single gestational week 14.5 human neocortical specimen. The hypothesis tested with this dataset was that a transcriptional signature of radial glia (neural stem cells) could be isolated via unsupervised gene coexpression analysis due to variation in the abundance of this cell type from section to section. This dataset is the first of its kind generated using this method (Gene Coexpression Analysis of Serial Sections, or GCASS).
Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.
Age, Specimen part
View SamplesIdentifying sex differences in gene expression within the brain is critical for determining why multiple neurological and behavioral disorders differentially affect males and females. Several are more common or severe in males (e.g., autism and schizophrenia) or females (e.g., Alzheimer’s disease and depression). We analyzed transcriptomic data from the mouse hippocampus of six inbred strains (129S1/SvImJ, A/J, C57BL/6J, DBA/1J, DBA/2J and PWD/Ph), to provide a perspective on differences between male and female gene expression. Our data show that: 1) significant gene expression differences in males versus females varies substantially across the strains, 2) 12 genes exist that are differentially expressed across the inbred strains (termed core genes), and 3) there are >2,600 significantly differentially expressed genes (DEGs) among the strains (termed non-core genes). We found that DBA/2J uniquely has a substantial majority (89%) of DEGs that are more highly expressed in females than males; 129/SvImJ is the most strongly male-biased with a majority (69%) of DEGs that are more highly expressed in males. To gain insight into the sex-biased DEGs, we examined gene ontology, pathway and phenotype enrichment and found significant enrichment in phenotypes related to abnormal nervous system morphology and physiology, among others. In addition, several pathways are enriched significantly, including Alzheimer’s disease (AD), with 32 genes implicated in AD, 8 of which are male-biased. Three of the male-biased genes have been implicated in a neuroprotective role in AD. Our transcriptomic data provide new insight into understanding the possible genetic bases for sex-specific susceptibility and severity of brain disorders. Overall design: Hippocampal mRNA from adult males and females of six inbred strains of mice were analyzed by RNA sequencing of 3 biological replicates using an Illumina HiSeq 2500
Transcriptomic analysis of the hippocampus from six inbred strains of mice suggests a basis for sex-specific susceptibility and severity of neurological disorders.
Sex, Age, Specimen part, Cell line, Subject
View SamplesTo explore the genome-wide gene expression changes induced by the K31R mutation in the histone H4 protein, we performed RNA-sequencing analysis in U2OS cells expressing either wildtype H4 or K31R mutant H4. We found that the lysine (K) to arginine (R) mutation mainly affected oxidative phosphorylation, mtiochondria dysfunction and et al, but not DNA damage signaling pathways. Overall design: Total RNAs were extracted from 3 wild-type (WT) H4 and 3 K31R mutant H4 expressing U2OS cells and profiled by RNA-sequencing.
UFL1 promotes histone H4 ufmylation and ATM activation.
Subject
View SamplesLong non-coding RNAs (lncRNAs) are a diverse category of transcripts with poor conservation and have expanded greatly in primates, particularly in their brain. We identified a lncRNA, which has acquired 16 microRNA response elements (MREs) for miR-143-3p in the Catarrhini branch of primates. This lncRNA termed LncND (neuro-development) gets expressed in neural progenitor cells and then declines in mature neurons. Binding and release of miR-143-3p, by LncND, can control the expression of Notch. Its expression is highest in radial glia cells in the ventricular and outer subventricular zones of human fetal brain. Down-regulation of LncND in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p over-expression and supported by RNA-seq analysis. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling in the expansion of the neural progenitor pool of primates and hence contributing to the rapid growth of the cerebral cortex. Overall design: Cerebral organoids were generated as in Lancaster et al. (Lancaster and Knoblich, 2014). Organoids were dissociated into single cells and captured on C1 Single-Cell Auto Prep Integrated Fluidic Circuit (IFC) (Fluidigm). The RNA extraction and amplification was performed on the chip as described by the manufacturer. We captured 68 single-cells on a C1 Single-Cell Auto Prep System (Fluidigm) and sequenced the RNA on a NextSeq500 System (Illumina) (Pollen et al., 2014). Out of 68 cells, we obtained 60 high quality cells.
A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA.
No sample metadata fields
View SamplesWe performed Fluidigm C1 single cell sequencing analysis of wild-type and microRNA deficient (Dgcr8 knockout) mouse embryonic stem cells mock treated or transfected with either miR-294 or let-7. Overall design: Wild-type and Dgcr8 knockout cells grown in naïve culture conditions were mock transfected or transfected with miRNA mimics for let-7b or miR-294, single cells were captured on Fluidigm C1 24 hours post-transfection and then prepared for sequencing on Illumina HiSeq1000 following manufacturer''s protocol.
The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells.
Specimen part, Subject
View Samples