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Homo sapiens
40 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Although corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy.
Publication Title
Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate from normal stem cells based on initiation of a de novo stem cell program, by reprogramming of a more differentiated cell type by oncogenic insults or both remains unresolved. A major hurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. We present evidence that normal and human telomerase reverse transcriptase (hTERT)-immortalized human mammary epithelial cells (hMECs) isolated and maintained in DFCI-1 medium retain a fraction with progenitor cell properties. These cells co-express basal, luminal and stem/progenitor cell markers. Clonal derivatives of progenitors co-expressing these markers fall into two distinct types: K5+/K19- (Type I) and K5+/K19+ (Type II). We show that both types of progenitor cells have self-renewal and differentiation ability. Through microarray analysis, we want to identify genes and pathways linked to human mammary epithelial stem/progenitor cell self-renewal and differentiation.
Publication Title
Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
Illumina HiSeq 2000
Description
Objective: Long non-coding RNAs (lncRNA) regulate gene transcription and diverse cellular functions. We previously defined a novel core inflammatory and metabolic ileal gene signature in treatment naïve pediatric Crohn Disease (CD), however, genome-wide characterization of lncRNA expression was lacking. We now extend our analyses to define a more comprehensive view that includes lncRNA. Design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RT-PCR was used to test lncRNAs regulation by IL-1ß in Caco-2 enterocytes model. Results: We characterize a widespread dysregulation of 459 lncRNA in the ileum of treatment naïve pediatric CD patients. Unsupervised and supervised classifications using the 459 lncRNA showed comparable patients' grouping as the 2160 dysregulated protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types showed that the up-regulated LINC01272 is associated with a myeloid pro-inflammatory signature while the down-regulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We further validated expression and regulation of prioritized lncRNA upon IL-1ß exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusion: We define differentially expressed lncRNA in the ileum of treatment naive pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNA, after mechanistic exploration, may serve as potential new targets for RNA-based interventions. Overall design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 21 days differentiated caco-2 cells
Publication Title
Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The spatial and temporal control of Hox gene transcription is essential for patterning the vertebrate body axis. Although this process involves changes in histone posttranslational modifications, the existence of particular three-dimensional (3D) architectures remained to be assessed in vivo. Using high-resolution chromatin conformation capture methodology, we examined the spatial configuration of Hox clusters in embryonic mouse tissues where different Hox genes are active. When the cluster is transcriptionally inactive, Hox genes associate into a single 3D structure delimited from flanking regions. Once transcription starts, Hox clusters switch to a bimodal 3D organization where newly activated genes progressively cluster into a transcriptionally active compartment. This transition in spatial configurations coincides with the dynamics of chromatin marks, which label the progression of the gene clusters from a negative to a positive transcription status. This spatial compartmentalization may be key to process the collinear activation of these compact gene clusters.
Publication Title
The dynamic architecture of Hox gene clusters.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 172 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was isolated from rectal biopsies from 190 pediatric patients undergoing diagnostic colonoscopy for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Single-end, 75-bp sequencing was performed, and raw reads aligned to the human genome using Gencode v 24 as reference. We included 14085 protein-coding mRNA genes in downstream analyses, where cutoffs of fold change>1.5 and FDR<0.05 were considered significant. Overall design: RNA-sequencing of rectal biopsies obtained from pediatric IBD and control patients.
Publication Title
Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD4+ cells from Foxp3.eGFP mice containing Foxp3- Teff and Foxp3+ Treg cells were treated with anti-CD3/CD28 monoclonal antibodies or soluble OX40L and JAG1 for 3 days to induce TCR-dependent vs TCR-independent Treg proliferation. Untreated fresh CD4+ T-cells used as control. Post treatment T-cell proliferation was confirmed by Cell Trace violet dilution and Foxp3+ (Treg) and Foxp3-(Teff) were sorted. Differential gene expression profiling between Tregs and Teff cells among control, anti-CD3/CD28 and OX40L-JAG1 treated cultured was performed using affymetrix mouse gene 2.0 ST micro array.
Publication Title
OX40L-JAG1-Induced Expansion of Lineage-Stable Regulatory T Cells Involves Noncanonical NF-κB Signaling.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Overall design: Transcriptional activity at the HoxD locus in the murine developing gut at E13, Differential gene expression analysis along the murine developing gut
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
SRP018708- Mus musculus
- 1 Downloadable Sample
- Illumina Genome Analyzer II
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Transcriptional activity at the HoxD locus in developing caeca at E13.5 Overall design: Transcriptional activity at the HoxD locus in developing caeca at E13.5
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Mechanical cues influence the shape, growth, and function of tissues and organs and are necessary for the development of engineered tissues. Yet, how cells sense mechanical cues and transduce them into changes in gene expression is not well understood. It is known that mechanical forces transmitted to the nucleus induce chromatin remodeling, promote DNA repair, contribute to the motion of intranuclear organelles and cause direct dissociation of protein complexes inside nuclei. Yet, the extent to which such signals impact gene expression is not understood. Because mechanical forces from the cytoskeleton to the nucleus interior are transmitted by the LINC (linker of nucleoskeleton-to-cytoskeleton) complex, we disrupted the LINC complex and performed genome wide expression studies using RNA sequencing. LINC disruption altered the expression of hundreds of genes at a genome-wide scale. We asked how LINC disruption affected the mechanosensitivity of individual genes by quantifying fold changes in gene expression on soft and stiff substrates. Remarkably, LINC disruption tended to preserve gene mechanosensitivity, but to reverse its direction. LINC disruption did not cause changes in nuclear shape, nor eliminated nuclear shape sensitivity to substrate rigidity. Our results show for the first time that the LINC complex regulates mechano-sensing at a genome-wide level, and argue for a distinct mechanism that does not require changes in nuclear morphology. Overall design: mRNA profiles of NIH 3T3 TetON cells that were induced to express either SS-GFP-KDEL (control) or SS-HA-Sun1L-KDEL by the addition of doxycycline. Two (2) substrate stiffnesses were used (1 kPa and 308 kPa), Y27632 or blebbistatin was used for certain samples to inhibit myosin II activity. A total of 6x3 reps= 18 samples were analyzed.
Publication Title
The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The majority of NK cells (~90%) are phenotypically characterized as CD56dimCD16+, while the remaining are CD56brightCD16-. The cytotoxic CD56dimCD16+ NK subset expresses higher levels of chemokine receptors, and therefore is preferentially recruited to sites of inflammation. Encounters between CD56dimCD16+ NK cells with target cells and locally secreted inflammatory cytokines synergize to induce activation of this subset, leading to dramatically increased cytotoxic activity against target cells and abundant pro-inflammatory cytokine production often equivalent to that of the CD56brightCD16- population. The early recruitment of activation of CD56dimCD16+ NK cells to sites of inflammation raises many important questions regarding the potential immune functions of these cells that extend beyond their cytotoxic capabilities. This study has sought to elucidate the genetic profile of activated CD56dimCD16+ NK cells via a series of laboratory-based approaches coupled with a bioinformatics persective.
Publication Title
Gene expression profiling of the human natural killer cell response to Fc receptor activation: unique enhancement in the presence of interleukin-12.
Sample Metadata Fields
Specimen part, Subject
View Samples