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GSE59843
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The oral cavity is the persistent reservoir for EBV with lifelong infection of resident epithelial and B cells. Infection of these cell types results in distinct EBV gene expression patterns that are regulated by epigenetic modifications involving DNA methylation and chromatin structure. Such regulation of EBV gene expression relies on viral manipulation of the host epigenetic machinery that may inadvertently result in long-lasting, oncogenic host epigenetic reprogramming. To test this hypothesis in the context of EBV infection of epithelial cells, we established a transient infection model to identify the epigenetic consequences after EBV infection of immortalized normal oral keratinocytes and subsequent viral loss.
Publication Title
Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 69 Downloadable Samples
NextSeq 500
Description
The rapid improvements in single cell sequencing technologies and analyses methods afford greater scope for dissecting organoid cultures composed of multiple cell types and create an opportunity to interrogate these models to understand tissue biology, cellular behaviour and interactions. To this end, retinal organoids generated from human embryonic stem cells (hESCs) were analysed by single cell RNA-Sequencing at three time points of differentiation. Combinatorial data from all time points revealed the presence of nine clusters, five of which corresponded to key retinal cell types, namely retinal pigment epithelium (RPE), retinal ganglion cells (RGCs), cone and rod photoreceptors and Müller glia cells. The remaining four clusters expressed genes typical of mitotic cells, extracellular matrix (ECM) components and those involved in retinal homeostasis. The cell clustering analysis revealed the decreasing presence of mitotic cells and RGCs, formation of a distinct RPE cluster, the emergence of cone and rod photoreceptors from photoreceptor precursors and an increasing number of Müller Glia cells over time. The pseudotime analysis resembled the order of cell birth during retinal development, with the mitotic cluster commencing the trajectory and the large majority of Müller glia being the latest. Together, these data demonstrate the feasibility and potential of single cell RNA-Seq to dissect the inherent complexity of the organoids and the orderly birth of key retinal cell types. Overall design: A hESC (H9) cell line harbouring a CRX-GFP reporter was differentiated to retinal organoids 25. Samples were collected at 60, 90 and 200 days, dissociated, partitioned into single cells using the Fluidigm C1 Single-Cell mRNA-Seq HT IFC and processed for scRNA-Seq.
Publication Title
Deconstructing Retinal Organoids: Single Cell RNA-Seq Reveals the Cellular Components of Human Pluripotent Stem Cell-Derived Retina.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Homo sapiens
- 96 Downloadable Samples
- NextSeq 500
Description
Death of photoreceptors and/or Retinal Pigment Epithelium (RPE) cells is a common cause of age related and inherited retinal dystrophies, thus their replenishment from renewable stem cell sources is a well sought therapeutic goal. Human pluripotent stem cells provide a useful cell source in view of their limitless self-renewal capacity and potential to differentiate into all key retinal cell types either in isolation or as part of three dimensional retinal organoids. Photoreceptor precursors have been isolated from differentiating human pluripotent stem cells either through application of cell surface markers or fluorescent reporter approaches and shown to share a transcriptional profile akin to foetal photoreceptors. In this study we investigated the transcriptional profile of CRX+ photoreceptor precursors derived from human embryonic stem cells (hESC) using single cell RNA sequencing and their engraftment capacity in an animal model of retinitis pigmentosa (C3H/rd1). Single cell RNA seq analysis revealed the presence of dominant cell cluster which displayed the hallmarks of early cone photoreceptor expression. When transplanted subretinally into the C3H/rd1 mice, the Crx positive cells settled next to the inner nuclear layer of host retina, matured into cone photoreceptors and made connections with the inner neurones of the host retina. Cellular transfer between the host retina and donor photoreceptors was investigated and shown to be minimal. Together our data provide valuable molecular insights into the transcriptional profile of human pluripotent stem cells derived CRX+ photoreceptor precursors and indicate their usefulness as a source of transplantable cone photoreceptors. Overall design: CRX-GFP human ESC line was differentiated to retinal organoids. At day 90 CRX+ and CRX- cells were purified by flow activated cell sorting and subjected to single cell RNA-seq. RNA-seq of bulk CRX+ and CRX- from the same experiment was carried out in parallel.
Publication Title
CRX Expression in Pluripotent Stem Cell-Derived Photoreceptors Marks a Transplantable Subpopulation of Early Cones.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We have investigated the regulation of anchorage-independent growth (AIG) by basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) in JB6 mouse epidermal cells in the context of wound repair versus carcinogenesis responses. bFGF induces an unusually efficient but reversible AIG response, relative to TPA-induced AIG which is irreversible. Distinct global gene expression profiles are associated with anchorage-independent colonies arising from bFGF-stimulated JB6 cells, relative to colonies arising from fully tumorigenic JB6 cells (RT101), including genes exhibiting reciprocal regulation patterns. Thus, while TPA exposure results in commitment to an irreversible and tumorigenic AIG phenotype, the AIG response to bFGF is reversible with essentially complete restoration of normal cell cycle check point control following removal of bFGF from growth medium. These results are consistent with the physiological role of bFGF in promoting wound healing, and suggest that natural mechanisms exist to reverse transformative cellular phenotypes associated with carcinogenesis.
Publication Title
Cellular dichotomy between anchorage-independent growth responses to bFGF and TPA reflects molecular switch in commitment to carcinogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Using a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Publication Title
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences of the exposure to bisphenol-A during development in pancreatic beta-cell growth
Publication Title
Maternal Exposure to Bisphenol-A During Pregnancy Increases Pancreatic β-Cell Growth During Early Life in Male Mice Offspring.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiScanSQ
Description
Phenotypic changes induced by extracellular vesicles (EVs) have been implicated in the recovery of acute kidney injury (AKI) induced by mesenchymal stromal cells (MSCs). miRNAs are potential candidates for cell reprogramming towards a pro-regenerative phenotype. The aim of the present study was to evaluate whether miRNA de-regulation inhibits the regenerative potential of MSCs and derived-EVs in a model of glycerol-induced AKI in SCID mice. For this purpose, we generated MSCs depleted of Drosha, a critical enzyme of miRNA maturation, to alter miRNA expression within MSCs and EVs. Drosha knock-down MSCs (MSC-Dsh) maintained the phenotype and differentiation capacity. They produced EVs that did not differ from those of wild type cells in quantity, surface molecule expression and internalization within renal tubular epithelial cells. However, EVs derived from MSC-Dsh (EV-Dsh) showed global down-regulation of miRNAs. Whereas, wild type MSCs and derived EVs were able to induce morphological and functional recovery in AKI, MSC-Dsh and EV-Dsh were ineffective. RNA sequencing analysis showed that genes deregulated in the kidney of AKI mice were restored by treatment with MSCs and EVs but not by MSC-Dsh and EV-Dsh. Gene Ontology analysis showed that down-regulated genes in AKI were associated with fatty acid metabolism. The up-regulated genes in AKI were involved in inflammation, ECM-receptor interaction and cell adhesion molecules. These alterations were reverted by treatment with wild type MSCs and EVs, but not by the Drosha counterparts. In conclusion, miRNA depletion in MSCs and EVs significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of miRNAs. Overall design: RNA-seq
Publication Title
AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Brown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue are important components of energy expenditure. An RNAseq-based analysis of the mouse BAT transcriptome led us to identify GPR120 as a gene induced by thermogenic activation. GPR120, a G protein-coupled receptor binding unsaturated long-chain fatty acids, is known to mediate some beneficial metabolic actions of polyunsaturated fatty acids. We show that pharmacological activation of GPR120 induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired browning in response to cold. n-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF-21) by brown and beige adipocytes and increases blood FGF21 levels. The effects of GPR120 activation are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 constitutes a novel pathway of brown fat activation and involves FGF21. Overall design: eight adult male C57BL6 mice were maintained at thermoneutral temperature (29C). After two weeks, a subset of four mice was placed at 4C environment temperature for 24h. RNAseq was performed on the BAT tissues of these 2 groups.
Publication Title
The kallikrein-kinin pathway as a mechanism for auto-control of brown adipose tissue activity.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Strategies to enhance islet b-cell survival and regeneration while refraining inflammation through manipulation of molecular targets would provide means to stably replenish the deteriorating functional b-cell mass detected in both Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM). Herein we report that over expression of the islet enriched transcription factor Pax4 refrains development of hyperglycemia in the RIP-B7.1 mouse model of T1DM through reduced insulitis, decreased b-cell apoptosis correlating with diminished DNA damage and increased proliferation. Transcriptomics revealed up regulation of genes involved in immunomodulation, cell cycle and ER homeostasis in islets over expressing Pax4 as compared to the T2DM-linked mutant variant Pax4R129W. Pax4 but not Pax4R129W protected islets from thapsigargin-mediated ER-stress apoptosis. Collectively, Pax4 is a critical signaling hub coordinating regulation of distinct molecular pathways resulting in improved b-cell fitness whereas Pax4R129W sensitizes to death under stress. More importantly we highlight potential common pharmacological targets for the treatment of DM.
Publication Title
PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples