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Homo sapiens
7 Downloadable Samples
IlluminaHiSeq2000
Description
Neuronal migration defects (NMDs) are among the most common and severe brain abnormalities in humans. Lack of disease models in mice or in human cells has hampered the identification of underlying mechanisms. From patients with severe NMDs we generated iPSCs then differentiated neural progenitor cells (NPCs). On artificial extracellular matrix, patient-derived neuronal cells showed defective migration and impaired neurite outgrowth. From a cohort of 107 families with NMDs, sequencing identified two homozygous C-terminal truncating mutations in CTNNA2, encoding aN-catenin, one of three paralogues of the a-catenin family, involved in epithelial integrity and cell polarity. Patient-derived or CRISPR-targeted CTNNA2- mutant neuronal cells showed defective migration and neurite stability. Recombinant aN-catenin was sufficient to bundle purified actin and to suppress the actin-branching activity of ARP2/3. Small molecule inhibitors of ARP2/3 rescued the CTNNA2 neurite defect. Thus, disease modeling in human cells could be used to understand NMD pathogenesis and develop treatments for associated disorders. Overall design: 2 biological replicates per individual (2 iPSC clone differentiations), excluding 1263A, which has one sample
Publication Title
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Majority of pancreatic cancer (PDAC) patient deaths are associated to the metastatic progression of disease. To identify novel targeted-therapies, a complete understanding of transformation in genetic landscape in tumors during disease progression is needed. Widely in use, the artificially immortalized PDAC cell lines do not rightly represent the progression because of multiple donors and disparate genetic characteristics. To identify key genes underlying the progression of PDAC from localized disease to a metastatic form, we performed whole transcriptome RNA-Sequencing analysis of cell models representing localised to metaststic stage through paired-end deep sequencing Method: Mouse expressing a Cre-activated KrasG12D allele inserted into the endogenous Kras locus, and these mice were crossed with mice expressing Cre recombinase in pancreatic tissue by virtue of a PDX-1 promoter-driven transgene. Next a cross between K-rasG12D Pdx-Cre and p16-/- mice, transgenic K-rasG12D Pdx-Cre p16-/- mice were generated harboring tissue specific mutant Kras and p16 deletion resulting in an earlier appearance of PanIN lesions followed by rapid progression into highly invasive and metastatic pancreatic cancers. Results: Transgenic K-rasG12D Pdx-Cre p16-/- mice developed spontaneous- localized, invasive and metastatic pancreatic tumors and transcriptome of these cell models representing localized, invasive and metastatic pancreatic tumors were sequenced. Conclusions: Based on genetic analysis of a same-lineage genetic background cell models, this study identifies a novel molecular pathway underlying the progression of pancreatic cancer disease. This study shows that Intestine Specific Homeobox (ISX) gene is a novel biomarker unique to pancreatic cancer progression. Overall design: By using tumors from K-rasG12D/p16-/- transgenic mice, we generated a spectrum of spontaneous (without immortalization) murine cell models representing localized (HI-Panc-L), invaise (HI-Panc-I) and metastatic (HI-Panc-M) stages. HI-Panc progression model is a valuable tool and by studying gene expression during progression of pancaretic cancer from localised to metaststic stage in a genetically same linaege wll be beneificail for pancartic cancer reaserch.
Publication Title
Characterization of Novel Murine and Human PDAC Cell Models: Identifying the Role of Intestine Specific Homeobox Gene ISX in Hypoxia and Disease Progression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
The conserved multi-subunit Ccr4-Not complex regulates gene expression in diverse ways. In this work, we characterize the suppression of temperature sensitivity associated with a mutation in the gene encoding the scaffold subunit of the Ccr4-Not complex, NOT1, by the deletion of SPT3.
Publication Title
A SAGA-independent function of SPT3 mediates transcriptional deregulation in a mutant of the Ccr4-not complex in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 91 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples
GSE8488- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Objectives: To identify similarities and differences in gene expression data in the MEK/ERK and PI3K pathways and to determine how histone modification affects these same pathways.
Publication Title
Regulation of gene expression by PI3K in mouse growth plate chondrocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-B and interferon signaling. Mice lacking the IKK kinase TAK1, showed normal positive selection, but a specific block in functional maturation. NF-B signaling provided protection from TNF, and was required for proliferation and emigration. Alternatively, the interferon signature was independent of NF-B, and IFNR deficient thymocytes showed reduced STAT1 levels and phenotypic abnormality, but were competent to proliferate. Thus, both NF-B and tonic IFN signals are involved in the final maturation of thymocytes into nave T cells.
Publication Title
Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
The function and retention/reprogramming of epigenetic marks during the germline-to-embryo transition is a key issue in developmental and cellular biology, with relevance to stem cell programming and trans-generational inheritance. In zebrafish, DNAme patterns are programmed in transcriptionally-quiescent early cleavage embryos; paternally-inherited patterns are maintained, whereas maternal patterns are reprogrammed to match the paternal pattern. Here we show that a 'placeholder' nucleosome, containing the histone H2A variant H2A.Z(FV) and H3K4me1, occupies virtually all regions lacking DNAme in both sperm and cleavage embryos – residing at promoters encoding housekeeping and early embryonic transcription factors. Upon genome-wide transcriptional onset, genes with the Placeholder become either active H3K4me3-marked or silent H3K4me3/K27me3-marked (bivalent). Importantly, functional perturbation causing Placeholder loss confers DNAme acquisition, whereas acquisition/expansion of Placeholder confers DNA hypomethylation and improper gene activation. Thus, during transcriptionally quiescent stages (gamete-zygote-cleavage), an H2A.Z(FV)/H3K4me1-containing Placeholder nucleosome deters DNAme, poising parental genes for either gene-specific activation or facultative repression. Overall design: Transcript abundance was analyzed for zebrafish sperm, and cleavage stage embryos that were either wild type or mutant for the anp32e gene.
Publication Title
Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming.
Sample Metadata Fields
No sample metadata fields
View Samples