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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
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1 knockout mice displayed phenotypes similar to those observed on ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes. Overall design: Total RNA-seq from dissected regions of the digestive tract, from wild-type and percc1-/- mice.
Publication Title
Noncoding deletions reveal a gene that is critical for intestinal function.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
The aim of the study was to investigate whether environmental factors like S-adenosylmethionine (SAM) via affecting epigenome could alter cocaine-induced gene expression and locomotor sensitization in mice.
Publication Title
S-adenosylmethionine modifies cocaine-induced DNA methylation and increases locomotor sensitization in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We show that Bmx-deficiency reduces angiotensin II -induced cardiac hypertrophy and pathological gene expression
Publication Title
Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling.
Sample Metadata Fields
Sex
View Samples
GSE38457- Rattus norvegicus
- 12 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
Illumina ratRef-12 v1.0 expression beadchip
Description
We show that an excess of VEGF-B protects the heart via adaptive cardiac hypertrophy and increased coronary arterial reserve, and by inducing a shift from lipid to glucose metabolism.
Publication Title
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: In malaria, parasites of the genus Plasmodium elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. In a microarray analysis of pooled, activated CD4+ T cells from mice infected with P. chabaudi, we detected inducible expression of Csf1, which promotes macrophage proliferation. To better characterize Csf1-producing T cells, single-cell RNA-Seq was performed. Results: Robust Csf1 expression was detected in a subset of sampled CD4+ T cells (n = 14/35), whereas the remainder of cells had no detectable Csf1. Further, we identified ~ 400 genes that were differentially expressed between Csf1+ and Csf1- T cells. Conclusions: This work defines the transcriptional landscape of a subset of activated CD4+ T cells that produce the cytokine Csf1. These cells are expected to be important in infections with intracellular pathogens such as Plasmodium. Overall design: Antigen-experienced (CD11a+ CD49d+) CD4+ T cells were isolated by double-sorting from the blood of C57BL/6 adult female mice 6 days post-infection with Plasmodium chabaudi. Single cells were isolated and processed for RNA sequencing using a Fluidigm C1 integrated fluidic circuit chip. 35 biological replicates were analyzed.
Publication Title
Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cebpa is a gene known for its role in hematopoetic development. Though it is proven to be indispensible in myelopoesis, the details of the role played by Cebpa in dendritic cell development is fairly unknown. Steady state DC development can be modelled in vitro by treating Lin- HSPC with FLT3L.
Publication Title
TNFα Rescues Dendritic Cell Development in Hematopoietic Stem and Progenitor Cells Lacking C/EBPα.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Three HL cell lines (HD-MyZ, L-540 and HDLM-2) were used to investigate the effects of perifosine and sorafenib using in vitro assays analyzing cell growth, cell cycle distribution, gene expression profiling (GEP), and apoptosis. Western blotting (WB) experiments were performed to determine whether the two-drug combination affected MAPK and PI3K/AKT pathways as well as apoptosis. Additionally, the antitumor efficacy and mechanism of action of perifosine/sorafenib combination were investigated in vivo in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice using tumor growth rates and survival as endpoints. RESULTS: While perifosine and sorafenib as single agents exerted a limited activity against HL cells, exposure of HD-MyZ and L-540 cell lines, but not HDLM-2 cells, to perifosine/sorafenib combination resulted in synergistic cell growth inhibition (40% to 80%) and cell cycle arrest. Upon perifosine/sorafenib exposure, L-540 cell line showed significant levels of apoptosis (up to 70%, P .0001) associated with severe mitochondrial dysfunction (cytochrome c, apoptosis-inducing factor release and marked conformational change of Bax accompanied by membrane translocation). Apoptosis induced by perifosine/sorafenib combination did not result in processing of caspase-8, -9, -3, or cleavage of PARP, and was not reversed by the pan-caspase inhibitor Z-VADfmk, supporting a caspase-independent mechanism of cell death. In responsive cell lines, WB analysis showed that antiproliferative and pro-apototic events were associated with dephosphorylation of MAPK and PI3K/Akt pathways. GEP analysis of HD-MyZ and L-540 cell lines, but not HDLM-2 cells indicated that perifosine/sorafenib treatment induced upregulation of genes involved in amino acid metabolism and downregulation of genes regulating cell cycle, DNA replication and cell death. In addition, in responsive cell lines, perifosine/sorafenib combination strikingly induced the expression of tribbles homologues 3 (TRIB3) both in vitro and in vivo. Silencing of TRIB3 prevented cell growth reduction induced by perifosine/sorafenib treatment. In vivo, the combined perifosine/sorafenib treatment significantly increased the median survival of NOD/SCID mice xenografted with HD-MyZ cell line as compared to controls (81 vs 45 days, P .0001) as well as mice receiving perifosine alone (49 days, P .03) or sorafenib alone (54 days, P .007). In mice bearing subcutaneous nodules generated by HD-MyZ and L-540 cell lines but not HDLM-2 cell line, perifosine/sorafenib treatment induced significantly increased levels of apoptosis (2- to 2.5-fold, P .0001) and necrosis (2- to 8-fold, P .0001), as compared to controls or treatment with single agents. In addition, perifosine/sorafenib treatment had no effect on HDLM-2 nodules, but significantly reduced L-540 nodules with 50% tumor growth inhibition, compared to controls. CONCLUSIONS: Perifosine/sorafenib combination resulted in strong anti-HL activity both in vitro and in vivo. These results warrant clinical evaluation of perifosine/sorafenib combined-treatment in HL patients.
Publication Title
Perifosine and sorafenib combination induces mitochondrial cell death and antitumor effects in NOD/SCID mice with Hodgkin lymphoma cell line xenografts.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Three HL cell lines (HD-MyZ, L-540 and HDLM-2) were used to investigate the effects of perifosine and sorafenib using in vitro assays analyzing cell growth, cell cycle distribution, gene expression profiling (GEP), and apoptosis. Western blotting (WB) experiments were performed to determine whether the two-drug combination affected MAPK and PI3K/AKT pathways as well as apoptosis. Additionally, the antitumor efficacy and mechanism of action of perifosine/sorafenib combination were investigated in vivo in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice using tumor growth rates and survival as endpoints. RESULTS: While perifosine and sorafenib as single agents exerted a limited activity against HL cells, exposure of HD-MyZ and L-540 cell lines, but not HDLM-2 cells, to perifosine/sorafenib combination resulted in synergistic cell growth inhibition (40% to 80%) and cell cycle arrest. Upon perifosine/sorafenib exposure, L-540 cell line showed significant levels of apoptosis (up to 70%, P .0001) associated with severe mitochondrial dysfunction (cytochrome c, apoptosis-inducing factor release and marked conformational change of Bax accompanied by membrane translocation). Apoptosis induced by perifosine/sorafenib combination did not result in processing of caspase-8, -9, -3, or cleavage of PARP, and was not reversed by the pan-caspase inhibitor Z-VADfmk, supporting a caspase-independent mechanism of cell death. In responsive cell lines, WB analysis showed that antiproliferative and pro-apototic events were associated with dephosphorylation of MAPK and PI3K/Akt pathways. GEP analysis of HD-MyZ and L-540 cell lines, but not HDLM-2 cells indicated that perifosine/sorafenib treatment induced upregulation of genes involved in amino acid metabolism and downregulation of genes regulating cell cycle, DNA replication and cell death. In addition, in responsive cell lines, perifosine/sorafenib combination strikingly induced the expression of tribbles homologues 3 (TRIB3) both in vitro and in vivo. Silencing of TRIB3 prevented cell growth reduction induced by perifosine/sorafenib treatment. In vivo, the combined perifosine/sorafenib treatment significantly increased the median survival of NOD/SCID mice xenografted with HD-MyZ cell line as compared to controls (81 vs 45 days, P .0001) as well as mice receiving perifosine alone (49 days, P .03) or sorafenib alone (54 days, P .007). In mice bearing subcutaneous nodules generated by HD-MyZ and L-540 cell lines but not HDLM-2 cell line, perifosine/sorafenib treatment induced significantly increased levels of apoptosis (2- to 2.5-fold, P .0001) and necrosis (2- to 8-fold, P .0001), as compared to controls or treatment with single agents. In addition, perifosine/sorafenib treatment had no effect on HDLM-2 nodules, but significantly reduced L-540 nodules with 50% tumor growth inhibition, compared to controls. CONCLUSIONS: Perifosine/sorafenib combination resulted in strong anti-HL activity both in vitro and in vivo. These results warrant clinical evaluation of perifosine/sorafenib combined-treatment in HL patients.
Publication Title
Perifosine and sorafenib combination induces mitochondrial cell death and antitumor effects in NOD/SCID mice with Hodgkin lymphoma cell line xenografts.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples