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SRP150634
Homo sapiens
16 Downloadable Samples
Illumina HiSeq 2500, Ion Torrent Proton
Description
Extracellular vesicles (EVs) enable cell-to-cell communication in the nervous system essential for development and adult function. Endosomal Sorting Complex Required for Transport (ESCRT) complex proteins regulate EV formation and release. Recent work shows loss of function (LOF) mutations in, CHMP1A, which encodes one ESCRT-III member, cause autosomal recessive microcephaly with pontocerebellar hypoplasia in humans (Mochida et al., 2012). Here we show CHMP1A is required for maintenance of progenitors in human cerebral organoids and that mouse Chmp1a is required for progenitor proliferation in cortex and cerebellum and specifically for sonic hedgehog (SHH) mediated proliferation through SHH secretion. CHMP1A mutation reduces intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs), and EV release. SHH protein is present on a subset of EVs marked by a unique set of proteins we call ART-EVs. CHMP1A's requirement in formation of ART-EVs and other EVs provides a model to elucidate EV functions in multiple brain processes. Overall design: Gene expression profiling in a hiPSC WT line and a hiPSC CHMP1A null line. Comparative analysis by RNA-seq in hIPSCs and directed differentiation to cerebral organoids. Treatment with smoothened agonist (SAG) was used for examination of SHH dependent response in WT and CHMP1A null organoids.
Publication Title
The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 80 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Background: Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. Results: We estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%). Conclusion: We apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection. Overall design: Placental mRNA was sequenced on an Illumina GAIIx. Samples were derived from 4 human groups, 10 individuals per group, 2 samples per individual
Publication Title
Evaluating intra- and inter-individual variation in the human placental transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 15 Downloadable Samples
- IlluminaHiSeq2000
Description
The first embryonic cell divisions rely on maternally stored mRNA and proteins. The zygotic genome is initially transcriptionally silenced and activated later in a process called zygotic genome activation (ZGA). ZGA in any species is still a poorly understood process; the timing of transcription onset is controversial and the identity of the first transcribed genes unclear. Zebrafish, Danio rerio, is a rapidly developing vertebrate model, which is accessible to experimentation and global studies before, during and after ZGA. Overall design: To accurately determine the onset of ZGA and to identify the first transcripts in zebrafish, we developed a metabolic labeling method, utilizing the ribonucleotide analog 4-thio-UTP, which allows efficient and specific affinity purification of newly transcribed RNA. Using deep sequencing, we characterized the onset of transcription in zebrafish embryos at 128-, 256-, and 512-cell stages. We identified 592 nuclear-encoded zygotically transcribed genes, comprising 670 transcript isoforms. Mitochondrial genomes were highly transcribed at all time points. Further, bioinformatic analysis revealed an enrichment of transcription factors and miRNAs among the newly transcribed genes, suggesting mechanistic roles for the early genes that are required to activate subsequent gene expression programs in development. Interestingly, analysis of gene-architecture revealed that zygotically transcribed genes are often intronless and short, reducing transcription and processing time of the transcript. The newly generated dataset enabled us to compare zygotically transcribed genes over a broad phylogenetic distance with fly and mouse early zygotic genes. This analysis revealed that short gene length is a common characteristic for early zygotically expressed genes. However, we detected a poor level of overlap for shared orthologs.
Publication Title
The earliest transcribed zygotic genes are short, newly evolved, and different across species.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 2 Downloadable Samples
- Illumina HiSeq 1000
Description
Aim of this project was to determine the transcriptional response of the isolate PA30 to tap water and waste water.
Publication Title
Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 2 Downloadable Samples
- Illumina HiSeq 1000
Description
Aim of this project was to determine the transcriptional response of the isolate PA49 to tap water and waste water.
Publication Title
Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of the study was to identify in vivo spermatogonial gene expression within the context of their biological niche.
Publication Title
Screening for biomarkers of spermatogonia within the human testis: a whole genome approach.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with novel indole-2-carboxamide antivirals 205432 or 206381.
Publication Title
Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the expression profile of adult mice heterozygous for Pitx2 isoform C.
Publication Title
PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Colon cancers typically contain tumor cell populations with differential WNT signaling activity. Colon cancer cells with high WNT-activity have been attributed increase tumorigenic potential and stem cell characteristics.
Publication Title
Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Since the discovery of adult neural stem cells, their exact identity is still under discussion. Moreover, the lack of a reproducible procedure to purify neural stem cells prospectively rather than by growing them in vitro has so far precluded their study at the transcriptome level. Here we demonstrate a novel procedure to prospectively isolate neural stem cells from the adult mouse subependymal zone on the basis of their GFAP- and prominin1-expression by fluorescence-activated cell sorting. All self-renewing, multipotent stem cells are contained in this fraction at 70% purity. The stem cell identity of these double-positive cells is further demonstrated in vivo, by using a novel split-Cre-technology for fate mapping.
Publication Title
In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells.
Sample Metadata Fields
Specimen part
View Samples