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GSE54207
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We have undertaken a screen of mouse limb tendon cells in order to identify molecular pathways involved in tendon development. Mouse limb tendon cells were isolated based on Scleraxis (Scx) expression at different stages of development: E11.5, E12.5 and E14.5
Publication Title
Transcriptomic analysis of mouse limb tendon cells during development.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 12 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Cellular dedifferentiation signifies the withdrawal of cells from a specific differentiated state into a stem cell-like undifferentiated state. However, the mechanism of dedifferentiation remains obscure. We showed that mature adipocytes (MA) and follicular granulosa cells (GC), which have distinct functions in vivo, can dedifferentiate during culture in vitro and acquire multipotency.
Publication Title
Gene expression profiling in multipotent DFAT cells derived from mature adipocytes.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGF/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we used microarrays to identify genes whose expression is regulated by the JNK pathway during dorsal closure of the Drosophila embryo.
Publication Title
The Drosophila serine protease homologue Scarface regulates JNK signalling in a negative-feedback loop during epithelial morphogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 119 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels, including abdominal aortic aneurysm (AAA). We tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA. Using a genome-wide approach, we investigated the PVAT transcriptome of AAA in 30 patients with either large (55 mm) or small (<55 mm) aneurysm diameter. We performed a data adjustment step using the DaMiRseq R/Bioconductor package, to remove the effect of confounders as produced by high-throughput gene expression techniques. We compared PVAT of AAA with PVAT of not-dilated abdominal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We found highly consistent differences in PVAT gene expression clearly distinguishing PVAT of AAA from PVAT of not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. These changes did not systemically affect other abdominal adipose depots (omental or subcutaneous fat). We dissected putative mechanisms associated with PVAT involvement in AAA through a functional enrichment network analysis: both innate and adaptive immune-response genes along with genes related to cell-death pathways, metabolic processes of collagen, sphingolipids, aminoglycans and extracellular matrix degradation were strongly overrepresented in PVAT of AAA compared with PVAT of not-dilated aorta. Our results provide support to a possible role of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. These disease-specific expression signatures could help identifying pharmacological targets for preventing AAA progression.
Publication Title
Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
Illumina Genome Analyzer
Description
Oct4, Sox2, Klf4, and cMyc (OSKM) reprogram somatic cells to pluripotency. To gain a mechanistic understanding of their function, we mapped OSKM-binding, stage-specific transcription-factors (TFs), and chromatin-states in discrete reprogramming stages and performed loss- and gain-of-function experiments. We found that early in reprogramming OSK extensively bind somatic-enhancers and initiate their decommissioning by recruiting Hdac1. Concurrently, OSK engage other sites, including specific pluripotency-enhancers, and induce the relocation of somatic TFs to these sites and away from somatic-enhancers, extending somatic-enhancer decommissioning genome-wide. Pluripotency-enhancer selection early in reprogramming occurs predominantly at sites with high OSK-motif densities and requires collaborative binding by OSK. Most pluripotency-enhancers are selected later and occupied by OS and stage-specific-TFs like Esrrb. Overexpression of stage-specific-TFs influences reprogramming efficiency by changing OSK-occupancy, somatic-enhancer decommissioning, and pluripotency-enhancer selection. We propose that collaborative interactions among OSK and with stage-specific-TFs direct both somatic-enhancer decommissioning and pluripotency-enhancer selection, which drives the enhancer reorganization underlying reprogramming Overall design: RNA-seq
Publication Title
Cooperative Binding of Transcription Factors Orchestrates Reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 118 Downloadable Samples
- Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. Transcriptome analysis revealed a global down-regulation of physiological AJC gene expression in the SAE of healthy smokers (n=53) compared to healthy nonsmokers (n=59), an observation associated with changes in molecular pathways regulating epithelial differentiation such as PTEN signaling and accompanied by induction of cancer-related AJC genes. Genome-wide co-expression analysis identified a smoking-sensitive AJC transcriptional network. The overall expression of AJC-associated genes was further decreased in COPD smokers (n=23). Exposure of human airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC-related genes, accompanied by decreased transepithelial resistance. Thus, cigarette smoking alters the AJC gene expression architecture in the human airway epithelium, providing a molecular basis for the dysregulation of airway epithelial barrier function during the development of smoking-induced lung disease.
Publication Title
Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 36 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: study the role of MALT1 auto-proteolysis in T cell receptor mediated activation of NF-kB. Methods: Jurkat cells were generated that express wild type MALT1, the auto-cleavage deficient MALT1-R149A mutant, the catalytic inactive MALT1-C464A mutant or the R149A-C464A double mutant (RACA). Expression of endogenous MALT1 was inactivated using TALEN technology for the Jurkat cells expressing MALT1-R149A (JDM-RA) and MALT1-C464A (JDM-CA). Illumina HISeq 2000 deep sequencing was performed to determine the mRNA profiles for MALT1, JDM-RA, JDM-CA and RACA cells in unstimulated conditions or after treatment with 75ng/ml PMA and 150 ng/ml ionomycin for 3 or 18 hrs. Results: PMA ionomycin stimulation of the MALT1 auto-cleavage defective JDM-RA cells fails to activate NF-kB-dependent transcription like for the MALT1 catalytic inactive JDM-CA cells and the double RACA mutant cells. Conclusion: MALT1 autoproteolysis is essential for transcription of NF-kB target genes Overall design: mRNA profiles of Jurkat expressing MALT1, MALT1-R149A, MALT1-C464A and MALT1-R149A-C464A after 0, 3 and 18 hours of stimulation with PMA and Ionomycin were generated by deep sequencing, in duplicate, using Illumina HISeq 2000
Publication Title
MALT1 auto-proteolysis is essential for NF-κB-dependent gene transcription in activated lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The initiation of the mucosal immune response in Peyers patch (PP) relies on the sampling, processing and efficient presentation of foreign antigens by dendritic cells (DC). PP DC encompass five subsets, among which CD11b+ conventional DC (cDC) and LysoDC have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here, we have studied the genetic relatedness of the different subsets of PP cDC at steady state and under TLR7 ligand stimulation. We also provide the transcriptional profiles of subepithelial TIM-4- and interfollicular TIM-4+ macrophages.
Publication Title
Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple myeloma (MM)-induced osteoclast (OC) formation occurs in close contact with MM cell infiltration into the bone marrow (BM) due to the imbalance of the receptor activator of NF-kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio in favor of RANKL in the micorenvironment. Soluble factors including CCL3/MIP-1?, IL7 and IL-3 also contribute to the increased OC formation in MM.The immunomodulatory drugs (IMiDs) directly inhibit OCs, however their effect on the mechanisms involved in MM-induced OC formation are not known and have been investigated in this study. We found that both Lenalidomide (LEN) and Pomalidomide (POM), at concentration ranging reached in vivo, significantly blunted RANKL up-regulation normalizing the RANKL/OPG ratio in human BM osteoprogenitor cells (PreOBs) co-cultured with MM cells and inhibited CCL3/MIP-1? production by MM cells. The reduction of CD49d expression on MM cells, a molecule critically involved in RANKL up-regulation in the micorenvironment, accompanied this effect. Consistently the pro-osteoclastogenic property of the conditioned medium of MM cells co-cultured with PreOBs was reduced in the presence of both IMiDs. By microarray analysis we further investigated the effect of POM and LEN on the transcriptional profile of both MM cells and PreOBs. We found a significant down-regulation in MM cells, in addition to CD49d, of genes belonging to the adhesion molecules family such as ITGA8 and ICAM2 (CD102) induced by both IMiDs compounds. In conclusion our data suggest that POM and LEN inhibits MM-induced OC formation through the inhibition of RANKL/OPG ratio targeting the expression of adhesion molecules by MM cells.
Publication Title
Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 236 Downloadable Samples
- Illumina HiSeq 4000
Description
Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement. Overall design: Differentiated naïve human embryonic stem cells and naïve human embryonic stem cells at different passages (Exp1 for late passage, Exp2 for early passage) were subjected to single cell RNA sequencing by the Fluidigm C1 Single-Cell Auto Prep System.
Publication Title
Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.
Sample Metadata Fields
Specimen part, Subject
View Samples