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GSE93987
Homo sapiens
207 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3, and to a lesser extent in layer 5.
Publication Title
Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
Illumina HiSeq 2500
Description
Fragile X syndrome (FXS), the most common genetic form of intellectual disability in male, is caused by silencing of the FMR1 gene by hypermethylation of the CGG expansion mutation in the 5'UTR region of FMR1 in FXS patients. Here, we applied recently developed DNA methylation editing tools to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/sgRNA switched the heterochromatin status of the upstream FMR1 promoter to an active chromatin state restoring a persistent expression of FMR1 in FXS iPSCs. Neurons derived from methylation edited FXS iPSCs rescued the electrophysiological abnormalities and restored a wild-type phenotype upon the mutant neurons. FMR1 expression in edited neurons was maintained in vivo after engrafting into the mouse brain. Finally, demethylation of the CGG repeats in post-mitotic FXS neurons also reactivated FMR1. Our data establish demethylation of the CGG expansion is sufficient for FMR1 reactivation, suggesting potential therapeutic strategies for FXS. Overall design: RNA-seq of FXS iPSC and neurons derived from FXS iPSC infected with lentiviruses expressing dCas9-Tet1-P2A-tBFP (dC-T) and a mCherry-expressing sgRNA targeting CGG repeats.
Publication Title
Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profiling was carried out on peripheral blood leukocytes from 14 healthy older adults. The primary research question is whether gene expression differs in individuals experiencing chronically high levels of social isolation (by UCLA Loneliness Scale) vs chronically low levels of social isolation.
Publication Title
Social regulation of gene expression in human leukocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 19 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Insults to the cerebral cortex, such as trauma, ischemia or infections, may result in the development of epilepsy, one of the most common neurological disorders. Previous studies have suggested that perturbations in neurovascular integrity and breakdown of the blood-brain barrier (BBB) lead to neuronal hypersynchronization and epileptiform activity, but the underlying mechanisms are unknown. As with BBB opening, treatment with albumin or with TGF-1 results in the development of hypersynchronized epileptiform activity. Given the latent period before the appearance of epileptiform activity, we hypothesized the underlying mechanism is a transcriptional response which would be similar for BBB breakdown and exposure to albumin or TGF-1. In search of a common pathway and transcriptional activation pattern we performed a genome wide analysis. Genomic expression analyses demonstrated similar expression patterns for BBB opening, albumin and TGF-1 exposure. Most importantly, TGF- pathway blockers suppressed most albumin-induced transcriptional changes.
Publication Title
Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis?
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 68 Downloadable Samples
- Illumina HiSeq 2500
Description
Concerted efforts over past decades have established a thorough understanding of the canonical somatic DNA methylation landscape as well as its systematic misregulation across most human cancers. However, the underlying mechanism that directs this genome-scale transformation remains elusive, with no clear model for its acquisition or understanding of its potential developmental utility. Here we present base pair resolution analysis of global remethylation from the hypomethylated state of the preimplantation embryo into the early epiblast and extraembryonic ectoderm. We show that these two states acquire highly divergent genomic distributions: while the proximal epiblast establishes a canonical CpG-density dependent pattern found in somatic cells, the extraembryonic epigenome becomes substantially more mosaic. Moreover, this alternate pattern includes specific de novo methylation of hundreds of CpG island promoter containing genes that function in early embryonic development and are orthologously methylated across an extensive cohort of human cancers. From these data, we propose a model where the evolutionary innovation of extraembryonic tissues in eutherian mammals required cooption of DNA methylation-based suppression as an alternate pathway to the embryonically utilized Polycomb group proteins, which otherwise coordinate germ layer formation in response to extraembryonic cues at the onset of gastrulation. Moreover, we establish that this decision is made deterministically downstream of the promiscuously utilized, and frequently oncogenic, FGF signaling pathway and utilizes a novel combination of epigenetic cofactors. Recruitment of this silencing mechanism to developmental genes during cancer therefore reflects the misappropriation of an innate regulatory pathway that may be spontaneously sampled as an alternate epigenetic landscape within somatic cells. Overall design: Comparison of gene expression patterns in Extraembryonic Ectoderm and cancer
Publication Title
Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Islets are known to respond to changes in ambient glucose. To quantify the transcriptome-wide changes in ambient glucose, we compared transcriptome of islets exposed to low and high glucose. Overall design: Isolated islets from wild type male mice. Islets from adult males were pooled, cultured overnight in RPMI containing 11 mM glucose. The next day, all islets were starved in RPMI containing 2.8 mM glucose for 2 hours before stimulation with 2.8 mM glucose or 16.8 mM glucose for 12 hours. Islets were lysed in Trizol for RNA isolation and library construction.
Publication Title
The transcriptional landscape of mouse beta cells compared to human beta cells reveals notable species differences in long non-coding RNA and protein-coding gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 384 Downloadable Samples
- IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Single-cell expression profiling by RNA-Seq promises to exploit cell-to-cell variation in gene expression to reveal regulatory circuitry governing cell differentiation and other biological processes. Here, we describe Monocle, a novel unsupervised algorithm for ordering cells by progress through differentiation that dramatically increases temporal resolution of expression measurements. This reordering unmasks switch-like changes in expression of key regulatory factors, reveals sequentially organized waves of gene regulation, and exposes regulators of cell differentiation. A functional screen confirms that a number of these regulators dramatically alter the efficiency of myoblast differentiation, demonstrating that single-cell expression analysis with Monocle can uncover new regulators even in well-studied systems. Overall design: We selected primary human myoblasts as a model system of cell differentiation to investigate whether ordering cells by progress revealed new regulators of the process. We sequenced RNA-Seq libraries from each of several hundred cells taken over a time-course of serum-induced differentiation. Please note that this dataset is a single-cell RNA-Seq data set, and each cell comes from a capture plate. Thus, each well of the plate was scored and flagged with several QC criteria prior to library construction, which are provided as sample characteristics; CONTROL indicates that this library is a off-chip tube control library constructed from RNA of approximately 250 cells and ''DEBRIS'' indicates that the well contained visible debris (and may or may not include a cell). Libraries marked DEBRIS thus cannot be confirmed to come from a single cell.
Publication Title
The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- IlluminaHiSeq2000
Description
RNA-Sequencing analysis of 18 papillary thyroid carcinoma biopsies and of 4 healthy donors'' thyroids. In this analysis we assessed differential gene expression and investigated the mutational landscape in this tumor type. Analysis of gene fusion was also performed, leading to the identification of a novel chimeric transcript, potential driver in tumor initiation. Overall design: Total RNA isolated from 18 papillary thyroid carcinoma biopsies and 4 healthy donors'' thyroids.
Publication Title
New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
Description
Here we propose the direct conversion of human somatic cells into naive induced pluripotent cells (niPSC). Dataset: 7 expanded niPSC lines (4 from BJ cells, 1 from HFF-1, 1 from WI38, 1from IMR90), 1 freshly-isolated primary colonies of niPSC from BJ, 1 established naive embryonic line H9, 1 primed induced pluripotent cell line (from BJ), 1 sample of BJ fibroblasts, 1 sample of WI38 fibroblasts, 1 sample IMR90 fibroblasts.
Publication Title
Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- NextSeq 500
Description
Maddalena et al. showed that the limited DNA transfer capacity (~4.7kb) of adeno associated viral (AAV) vectors can be expanded up to 14kb with triple AAV vectors for the efficient expression of the therapeutic CDH23 (10.1kb) and ALMS1 (12.5kb) genes. Overall design: cells infected with triple AAV vectors carrying 2 different transgenes in 3 biological replicates; RNA extracted from WT cells was used as control .
Publication Title
Triple Vectors Expand AAV Transfer Capacity in the Retina.
Sample Metadata Fields
Cell line, Subject
View Samples