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SRP047233
Homo sapiens
54 Downloadable Samples
IlluminaHiSeq2000
Description
Truncating mutations of CHD8, encoding a chromodomain helicase, and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA-seq) with genome-wide CHD8 binding (ChIP-seq). Suppressing CHD8 to levels comparable with loss of a single allele caused altered expression of 1,756 genes, 64.9% of which were up-regulated. CHD8 showed widespread binding to chromatin, with 7,324 replicated sites that marked 5,658 genes. Integration of these data suggests that a limited array of direct regulatory effects of CHD8 produced a much larger network of secondary expression changes. Genes indirectly down-regulated (i.e., without CHD8 binding sites) reflect pathways involved in brain development, including synapse formation, neuron differentiation, cell adhesion, and axon guidance, whereas CHD8-bound genes are strongly associated with chromatin modification and transcriptional regulation. Genes associated with ASD were strongly enriched among indirectly down-regulated loci (p = 1.01x10-9) and CHD8-bound genes (p = 4.34x10-3), which align with previously identified co-expression modules during fetal development. We also find an intriguing enrichment of cancer related gene-sets among CHD8-bound genes (p < 1.9x10-11). In vivo suppression of chd8 in zebrafish produced macrocephaly comparable to that of humans with inactivating mutations. These data indicate that heterozygous disruption of CHD8 precipitates a network of gene expression changes involved in neurodevelopmental pathways in which many ASD-associated genes may converge on shared mechanisms of pathogenesis. Overall design: RNA-seq in NPCs treated with shRNAs targeting CHD8. For controls, NPCs were treated with shRNAs targeting GFP and LacZ. Infection and sequencing was carried out in two separate batches, with one GFP and one LacZ sample in each batch. All samples were sequenced in two technical replicates.
Publication Title
CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 99 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The 600kb BP4-BP5 16p11.2 CNV (copy number variant) is associated with neuroanatomical, neurocognitive and metabolic disorders. These recurrent rearrangements are associated with reciprocal phenotypes such as obesity and underweight, macro- and microcephaly, as well as autism spectrum disorder (ASD) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal CNVs in 16p11.2.
Publication Title
A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Caenorhabditis elegans
- 217 Downloadable Samples
- Illumina HiSeq 2500
Description
A prevalent hypothesis for the cell-to-cell coordination of the phenomena of early development is that a defined mixture of different mRNA species at specific abundances in each cell determines fate and behavior. With this dataset we explore this hypothesis by quantifying the abundance of every mRNA species in every individual cell of the early C. elegans embryo, for which the exact life history and fate is precisely documented. Overall design: Embryos of the 1-, 2-, 4-, 8- and 16-cell stage were dissected into complete sets of single cells, and each cell from each set was sequenced individually using SMARTer technology. 5-9 replicates were generated for each stage. Most cell identities were unknown upon sequencing, but were deduced from by their transcriptomes post hoc.
Publication Title
A Transcriptional Lineage of the Early C. elegans Embryo.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Expression of the MT1-MMP gene induces a significant upregulation of of oncogenes and tumorignenic genes in 184B5-MT1 cells.
Publication Title
Membrane type-1 matrix metalloproteinase confers aneuploidy and tumorigenicity on mammary epithelial cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive metastatic niches within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.
Publication Title
Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In order to obtain a global picture regarding regulation of p53 in liver cells we used HepG2 hepatoma cells.We created two isogenic sub-cultures of HepG2 cells with altered expression of p53.
Publication Title
Chemotherapeutic agents induce the expression and activity of their clearing enzyme CYP3A4 by activating p53.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 1113 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We successfully sequenced and annotated more than 400 cells from child, adult control, type 1 diabetes and type 2 diabetes donors. We detect donor-type specific transcript variation. We also report that cells from child donors have less defined gene signature. Cells from type 2 diabetes donors resemble juvenile cells in gene expression. Overall design: Cells from three adult controls (56, 74, 92), one donor with type 1 diabetes (91), two donors with type 2 diabetes (75, 143), and two child donors (40, 72) were sequenced. Numbers in parathesis indicates number of cells sequenced.
Publication Title
Single-Cell Transcriptomics of the Human Endocrine Pancreas.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown.
Publication Title
Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Recently, a frequent chromosomal aberration fusing Androgen regulated TMPRSS2 promoter and the ERG gene (T/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between the T/ERG and other defective pathways in cancer progression however, the biological mechanism by which the T/ERG operates is yet to be determined. Using immortalized prostate epithelial cells (EP) model we were able to show that EP with the combination of androgen receptor(AR) and T/ERG(EP-AR T/ERG cell line) demonstrate an Epithelial to Mesenchymal Transition (EMT) manifested by a mesenchyme-like morphological appearance and behavior.
Publication Title
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Cancer stem cell (CSC) identification relies on transplantation assays of cell sub-populations sorted from fresh tumor samples. Herein, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in-vivo propagating patient derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of EMT, invasion/motility, metastasis and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers. Overall design: Tumorigenic fractions from early-passaged PDX
Publication Title
In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.
Sample Metadata Fields
Subject
View Samples