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SRP193559
Homo sapiens
24 Downloadable Samples
Illumina HiSeq 2500, NextSeq 550
Description
Individuals with cystic fibrosis (CF) experience elevated inflammation in multiple organs, but whether this reflects an inherent feature of CF cells or is a consequence of a pro-inflammatory environment is not clear. Using CRISPR/Cas9-mediated mutagenesis of CFTR, 17 subclonal cell lines were generated from Caco-2 cells. Clonal lines with functional CFTR (CFTR+) were compared to those without (CFTR-) to directly address the role of CFTR in inflammatory gene regulation. All lines maintained CFTR mRNA production and formation of tight junctions. CFTR+ lines displayed short circuit currents in response to forskolin, while the CFTR- lines did not. Baseline expression of both cytokines was not different between the lines regardless of CFTR genotype. All lines responded to TNFa and IL1b by increasing IL6 and CXCL8 (IL8) mRNA levels, but the CFTR- lines produced more CXCL8 mRNA than the CFTR+ lines. Transcriptomes of 6 CFTR- and 6 CFTR+ lines, before and after stimulation by TNFa, were compared for differential expression as a function of CFTR genotype. While some genes appeared to be differentially expressed simply because of CFTR's absence, others required stimulation for differences to be apparent. Together, these data suggest cells respond to CFTR's absence by modulating transcriptional networks, some of which are only apparent when cells are exposed to different environmental contexts, such as inflammation. With regards to inflammation, these data suggest a model in which CFTR's absence leads to a poised, pro-inflammatory state of cells that is only revealed by stimulation. Overall design: Compare cells with intact CFTR to cells lacking CFTR for overall gene expression under basal and TNFa-stimulated conditions
Publication Title
Inactivation of CFTR by CRISPR/Cas9 alters transcriptional regulation of inflammatory pathways and other networks.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The generation of induced pluripotent stem (iPS) cells 1-4 has spawned unprecedented opportunities for investigating the molecular logic that underlies cellular pluripotency and reprogramming, as well as for obtaining patient-specific cells for future clinical applications. However, both prospects are hampered by the low efficiency of the reprogramming process. Here, we show that juvenile human primary keratinocytes can be efficiently reprogrammed to pluripotency by retroviral transduction with Oct4, Sox2, Klf4 and c-Myc. Keratinocyte-derived iPS (KiPS) cells appear indistinguishable from human embryonic stem (hES) cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, as well as in vitro and in vivo differentiation potential. Notably, keratinocyte reprogramming to pluripotency is, at least, 100-fold more efficient and 2-fold faster than that of fibroblasts. This increase in reprogramming efficiency allowed us to expand the practicability of the technology and to generate KiPS cells from single plucked hairs from adult individuals.
Publication Title
Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We analysed the RNA profile of IPSC-derived dopaminergic neurons from idiophatic and genetic form (LRRK2) of Parkinsons disease (PD). Both, idiopathic and genetic form of the disease show similar expression alterations and were merged in one whole PD group. We found 437 differentially expressed genes (DEGs) in the PD group as a whole. Up-regulated DEGs (n=254) encompassed genes involved in neural functions and transcription factor functions whereas down-regulated DEGs (n=183) affected basic homeostasis. These data point towards the presence of gene - and also protein - expression changes in DAn from PD patients which co-occur simultaneously along with DNA methylation changes.
Publication Title
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Numerous studies have described the altered expression and the causal role of miRNAs in human cancer. However, to date efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here, we find that Nucleolin (NCL), a major nucleolar protein, post-transcriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, causally involved in breast cancer initiation, progression and drug-resistance. We also show that NCL is commonly overexpressed in human breast tumors, and its expression correlates with that of NCL-dependent miRNAs. Finally, this study indicates that NCL-binding guanosine-rich aptamers affect the levels of NCL-dependent miRNAs and their target genes, reducing breast cancer cell aggressiveness, both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.
Publication Title
In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 251 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 251 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Publication Title
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene Expression Array (primeview), Illumina HumanHT-12 V4.0 expression beadchip, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the United States Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for sequence discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed, for these and qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcriptlevel profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.
Publication Title
A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. We made induced pluripotent stem cell (iPSC) lines from HD patients and controls. Though no obvious effects of the CAG expansion on reprogramming or subsequent neural stem cell (NSC) production were seen, HD-NSCs showed CAG expansion-associated gene expression patterns and, upon differentiation, changes in electrophysiology, metabolism, cell adhesion, and ultimately an increased risk of cell death for both medium and longer CAG repeat expansions, with some deficits greater in cells from longer repeat HD NSCs. The HD180 lines were more vulnerable than control lines to cellular stressors and BDNF withdrawal using a range of assays across consortium laboratories. This HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a novel human stem cell platform for screening new candidate therapeutics.
Publication Title
Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 325 Downloadable Samples
- Illumina HiSeq 2000
Description
In order to study parent-of-origin effects on gene expression, we performed RNAseq analysis (100bp single end reads) of 165 children who formed part of mother/father/child trios where genotype data was available from the HapMap and/or 1000 Genomes Projects. Based on phased genotypes at heterozygous SNP positions, we generated allelic counts for expression of the maternal and paternal alleles in each individual. This analysis reveals significant bias in the expression of the parental alleles for dozens of genes, including both previously known and novel imprinted transcripts. Overall design: This submission contains RNAseq data from 165 children from mother/father/child trios studied as part of the 1000 genomes and/or HapMap projects. We provide raw fastq format reads, and processed read counts per gene. Allelic count information can be provided by directly contacting the authors.
Publication Title
RNA-Seq in 296 phased trios provides a high-resolution map of genomic imprinting.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples