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SRP031980
Mus musculus
2 Downloadable Samples
Description
Our independent analyses using mRNA-Seq, quantitative RT-PCR, and in situ hybridization confirmed a significant up-regulation of Fezf2 in Tbr1-/- neocortex. However, analysis by immunostaining and immunoblotting revealed that SOX5 protein levels were relatively unaltered in late embryonic and neonatal Tbr1-/- cortex. This led us to the hypothesis that TBR1 regulates Fezf2 transcription via direct binding to regulatory sequences near Fezf2. To identify genome-wide TBR1 binding sites in an unbiased and hypothesis-independent manner, we analyzed TBR1-immu-noprecipitated chromatin using deep sequencing (ChIP-Seq). We tested several available anti-TBR1 antibodies and found that none was suitable for immunoprecipitating chromatin of sufficient quality for ChIP-Seq. Thus, we generated a V5-TBR1fusion construct and expressed it in N2A cells. V5-TBR1 was immunoprecipitated using an anti-V5 antibody. DNA-Seq was performed on the Illumina GAIIx platform.
Publication Title
TBR1 directly represses Fezf2 to control the laminar origin and development of the corticospinal tract.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
The hallmark of the cerebral neocortex is its organization into six distinct layers, each containing a characteristic set of neural cell types and synaptic connections. The transcriptional events involved in laminar development and function still remain elusive. Here we employed deep sequencing of mRNA and small RNA species to gain insights into transcriptional differences among layers and their temporal dynamics during postnatal development of the mouse primary somatosensory neocortex. A number of novel coding and noncoding transcripts were identified with specific spatiotemporal expression and splicing patterns across layers or time points. We also identified gene co-expression networks associated with distinct biological processes and transcriptional sharing between distinct biological processes, as well as, potential microRNA and mRNA interactions. Overall, this study provides an integrated view of the laminar and temporal expression dynamics of coding and noncoding transcripts in the mouse neocortex and a resource for future studies of neurodevelopment and transcriptome.
Publication Title
Laminar and temporal expression dynamics of coding and noncoding RNAs in the mouse neocortex.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
We employ mRNA-seq to investigate transcriptome of Pum1-Knockout, Pum2-Knockout and WT conditons Overall design: In order to investigate whether Pum1 and Pum2 regulate their targets at their RNA levels, we used 1/10 of the samples from the Pum1 and Pum2 iCLIP experiments (four biological repeats of WT, P1KO, and P2KO neonatal brains) to extract total RNAs for RNA deep sequencing. And we also collected three Ndcko neonatal brains for RNA deep sequencing.
Publication Title
Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 186 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Tissue was microdissected from 13 regions, including 9 distinct neocortical areas, from both left and right sides of four late second trimester human brain specimens. Gene- and exon-level differential expression analyses were performed by mixed model, nested analysis of variance using the XRAY software from Biotique Systems. Further details available in Johnson, Kawasawa, et al., "Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis" Neuron, Volume 62, Issue 4, 2009
Publication Title
Functional and evolutionary insights into human brain development through global transcriptome analysis.
Sample Metadata Fields
Age
View Samples- Sus scrofa
- 22 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Mouse bone marrow-derived macrophages (BMDM) grown in macrophage colony-stimulating factor (CSF-1) have been used widely in studies of macrophage biology and the response to toll-like receptor agonists. We investigated whether similar cells could be derived from the domestic pig. Cultivation of pig bone marrow cells for 5-7 days in presence of rhCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, CD163, CD172a), are potent phagocytic cells and produced tumor necrosis factor (TNF) in response to lipopolysaccharide (LPS). Bone marrow cells could be stored frozen and thawed, providing a renewable resource.
Publication Title
Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 116 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Trisomy 21 (Ts21) or Down syndrome (DS) is the most common genetic cause of intellectual disability. To investigate the consequences of Ts21 on human brain development, we have systematically analyzed the transcriptome of dorsolateral prefrontal cortex (DFC) and cerebellar cortex (CBC) using exon array mapping in DS and matched euploid control brains spanning from prenatal development to adulthood. We identify hundreds of differentially expressed (DEX) genes in the DS brains, many of which exhibit temporal changes in expression over the lifespan. To gain insight into how these DEX genes may cause specific DS phenotypes, we identified functional modules of co-expressed genes using several different bioinformatics approaches, including WGCNA and gene ontology analysis. A module comprised of genes associated with myelination, including those dynamically expressed over the course of oligodendrocyte development, was amongst those with the great levels of differential gene expression. Using Ts65Dn mouse line, the most common rodent model of DS, w e observed significant and novel defects in oligodendrocyte maturation and myelin ultrastructure; establishing a correlative proof-of-principle implicating myelin dysgenesis in DS. Thus, examination of the spatio-temporal transcriptome predicts specific cellular and functional events in the DS brain and is an outstanding resource for determining putative mechanisms involved in the neuropathology of DS.
Publication Title
Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination.
Sample Metadata Fields
Sex, Disease, Race
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2000
Description
A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the cerebrospinal fluid (CSF). To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) vs. fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system. Overall design: Two-factor design with two levels per factor and n=2 biological replicates. Lateral (telencephalic) and fourth (hindbrain) choroid plexus samples are paired in that they are isolated from the same brains.
Publication Title
Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2667 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The development of the human brain is a complex and precisely regulated process that unfolds over a protracted period of time. Human-specific features of this process, especially the ways in which highly complex neural circuits of the cerebral cortex form, are likely to be important factors in the evolution of human specializations. However, in addition to giving us remarkable cognitive and motor abilities, the formation of intricate neural circuits may have also increased our susceptibility to psychiatric and neurodegenerative disorders. Furthermore, substantial evidence suggests that the symptoms and progression of many brain disorders are dramatically influenced by genetic and developmental processes that define regional cell phenotypes and connectivity. Sex differences also play an important role in brain development and function and are a risk factor for several brain disorders, such as autism spectrum disorders (ASD) and depression. Thus understanding the spatiotemporal dynamics and functional organization of the brain transcriptome is essential to teasing out the keys to human neurodevelopment, sexual dimorphism, and evolution as well as our increased susceptibility to certain brain disorders. Most transcriptome studies of the developing brain have been restricted to rodents, and those performed in humans and nonhuman primates have included relatively small sample sizes and predominantly focused on few regions or developmental time points. Because many prominent features of human brain development significantly diverge from those of well-characterized model organisms, the translation of knowledge across species is difficult, and it is likely that many underlying genetic processes have gone undetected. In this study, we have taken a genome-wide approach to analyze the human transcriptome at single-exon resolution with ~1.4 million exon-level probe sets in 16 brain regions from donors representing both sexes and multiple ethnicities, across pre and postnatal development, including adolescence, and adulthood. We also generated genome-wide genotype data for 2.5 million single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for each specimen. Our analyses of the data revealed several features of the human brain transcriptome: spatiotemporal expression dynamics of individual and functionally related groups of genes, differential exon usage, sex-specific expression patterns and exon usage, and organization of the transcriptome into functional modules. We also profiled developmental trajectories of genes important for neurobiological themes and genes associated with ASD and schizophrenia. Finally, we present associations between specific SNPs and gene expression levels in different brain regions across development. The dataset presented here provides research opportunities and a wealth of information not previously available to the scientific community.
Publication Title
Spatio-temporal transcriptome of the human brain.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
From over 300 patients two groups were selected which had prostate tumors with either well differentiated (WD) or poorly differentiated (PD) after radical Prostatectomy. The PD group had Gleason score 8-9, seminal vesicle invasion, and poorly differentiated tumor cells; the WD group had Gleason score 6-7, no seminal vesicle invasion, and well to moderately differentiated tumor cells. LCM compatible specimens were selected from age and race (Caucasians) matched PD or WD patients with no family history of CaP. Matching normal epithelal cells were also selected for the analysis.
Publication Title
Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression profiling of mouse ing2 -/- testis vs WT reveals gene expression differences consistent with spermatogenic arrest and infertility. Ing2 is indispensable for male germ cell development in mice. While mice deficient for Ing2 were born and grew without apparent abnormalities, male, but not female, were infertile, consistent with the highest expression of Ing2 in testes in wild-type mice and in humans. Histological and DNA content analyses in Ing2-/- testes revealed a spermatogenesis arrest at meiotic phase and enhanced apoptosis associated with increased p53, resulting in a decline in mature spermatozoa, which became more severe in older age. HDAC1 accumulation and core histone deacetylation at pachytene stage were impaired in Ing2-/- testes, suggesting that the recruitment of HDAC1 by Ing2 plays a critical role in spermatogenesis. This study establishes Ing2 as a novel mammalian regulator of spermatocyte differentiation, which coordinates spermatogenesis stage-specific histone modifications. This study has implications in understanding human male infertility.
Publication Title
Targeted disruption of Ing2 results in defective spermatogenesis and development of soft-tissue sarcomas.
Sample Metadata Fields
Sex, Specimen part
View Samples