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GSE13824
Macaca mulatta
19 Downloadable Samples
Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
HIV-associated dementia (HAD) is a syndrome occurring in HIV-infected patients with advanced disease that likely develops as a result of macrophage and microglial activation as well as other immune events triggered by virus in the central nervous system. The most relevant experimental model of HAD, rhesus macaques exhibiting SIV encephalitis (SIVE), closely reproduces the human disease and has been successfully used to advance our understanding of mechanisms underlying HAD. In this study we integrate gene expression data from uninfected and SIV-infected hippocampus with a human protein interaction network and discover modules of genes whose expression patterns distinguish these two states, to facilitate identification of neuronal genes that may contribute to SIVE/HIV cognitive deficits. Using this approach we identify several downregulated candidate genes and select one, EGR1, a key molecule in hippocampus-related learning and memory, for further study. We show that EGR1 is downregulated in SIV-infected hippocampus and that it can be downregulated in differentiated human neuroblastoma cells by treatment with CCL8, a product of activated microglia. Integration of expression data with protein interaction data to discover discriminatory modules of interacting proteins can be usefully employed to prioritize differentially expressed genes for further study. Investigation of EGR1, selected in this manner, indicates that its downregulation in SIVE may occur as a consequence of the host response to infection, leading to deficits in cognition.
Publication Title
An integrated systems analysis implicates EGR1 downregulation in simian immunodeficiency virus encephalitis-induced neural dysfunction.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, while evidence supports the replicative capacity of adult beta cells in vivo, attempts at expanding human islet cells in tissue culture resulted in loss of beta-cell phenotype. Using a genetic lineage-tracing approach we have provided evidence for massive proliferation of beta-cell-derived (BCD) cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT). Epigenetic analyses indicate that key beta-cell genes maintain a partially open chromatin structure in expanded BCD cells, although they are not transcribed. Here we report that BCD cells can be induced to redifferentiate by a combination of soluble factors. The redifferentiated cells express beta-cell genes, store insulin in typical secretory vesicles, and release it in response to glucose. The redifferentiation process involves mesenchymal-epithelial transition, as judged from changes in gene expression. Moreover, inhibition of the EMT effector SLUG using shRNA results in stimulation of redifferentiation. BCD cells also give rise at a low rate to cells expressing other islet hormones, suggesting transition through an islet progenitor-like stage during redifferentiation. These findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for transplantation, as well as basic research, toxicology studies, and drug screening.
Publication Title
Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Access to an unlimited number of human pancreatic beta cells represents a major challenge in the field of diabetes to better dissect human beta cell functions and to make significant progress in drug discovery and cell replacement therapies. We previously reported the generation of the EndoC-bH1 human beta cell line that was generated by targeted oncogenesis in human fetal pancreases followed by in vivo cell differentiation in mice. Such cell line displayed many functional properties of adult beta cells. Here we devised a novel strategy to generate conditionally immortalized human beta cell lines based on CRE-mediated excision of immortalizing transgenes. The resulting EndoC-bH2 cell line can be massively amplified in vitro. Transgenes are next efficiently excised upon CRE expression leading to cell proliferation arrest and strong enhancement of beta cell specific features such as insulin expression, content and secretion. Excised EndoC-bH2 cells are close to authentic human beta cells and represent a unique tool to further study beta cell function and to understand why adult human beta cells are refractory to proliferation and how to achieve drug-dependent mobilization towards beta cell expansion.
Publication Title
Development of a conditionally immortalized human pancreatic β cell line.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Aims/hypothesis: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it.
Publication Title
Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
Illumina HiSeq 2000
Description
Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest Autism Spectrum Disorder (ASD) high-risk associated genes. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin-binding profile combined with transcriptome and chromatin accessibility analyses of Chd7-deleted OPCs, demonstrates that Chd7 protects non-proliferative OPCs from apoptosis by chromatin-closing and transcriptional repression of p53. Furthermore, Chd7 controls OPC differentiation through chromatin-opening and transcriptional activation of key regulators, including Sox10, Nkx2.2 and Gpr17. Chd7 is however dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by their common chromatin binding profiles and genetic interaction. Finally, CHD7 and CHD8 bind in OPCs to a majority of ASD-risk associated genes, suggesting an implication of oligodendrocyte lineage cells in ASD neurological defects. Our results thus offer new avenues to understand and modulate the CHD7 and CHD8 functions in normal development and disease. Overall design: RNA-seq from Chd7iKO and Control O4+ soted cells
Publication Title
Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 84 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We have previously identified hundreds of human islet lncRNAs. Here we functionally characterise 12 such lncRNAs in EndoC-betaH1 cells through loss of function studies.
Publication Title
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 14 Downloadable Samples
- NextSeq 500
Description
Plants are sessile organisms and therefore must sense and respond to changes of their surrounding conditions such as ambient temperature, which vary diurnally and seasonally. It is not yet clear how plants sense temperature and integrate this information into their development. We have previously shown that H2A.Z-nucleosomes are evicted in response to warmer temperatures. It is not clear however, whether the link between transcriptional responsiveness and changes in H2A.Z binding in context of temperature shifts is a global trend that can be seen throughout the genome, or the phenomenon is specific to a specialised set of temperature-responsive genes. In addition to the role of H2A.Z-nucleosome dynamics in the transcriptional response to temperature, it was shown that genes strongly misregulated in the h2a.z mutant are enriched for gene categories involved in response to multiple environmental cues. This suggests that H2A.Z could be implicated in the transcriptional response to various environmental inputs, raising the question: What brings the specificity of H2A.Z dynamics in response to temperature? To address this question we have profiled H2A.Z-nucleosome occupancy genome wide (using ChIP-seq) during a time course after temperature variation and compared its dynamics to transcriptional changes. We identified a fast, targeted and transient eviction of H2A.Z associated with transcriptional activation in response to temperature for a few hundreds genes. This eviction is associated with a reduction of the stability of the nucleosome. Moreover the genes with a fast H2A.Z eviction were strongly enriched in heat shock elements in their promoter and we observed a strong association between HSF1 binding and H2AZ eviction at warm temperature. These results highlight the importance of the interplay between transcription factors and chromatin to allow a controlled and dynamics response to temperature. Overall design: RNA-seq were generated in duplicate for seedlings shifted to warm temperature
Publication Title
Transcriptional Regulation of the Ambient Temperature Response by H2A.Z Nucleosomes and HSF1 Transcription Factors in Arabidopsis.
Sample Metadata Fields
Subject
View Samples- Arabidopsis thaliana
- 2 Downloadable Samples
- Illumina HiSeq 1000
Description
Plants are sessile organisms and therefore must sense and respond to changes of their surrounding conditions such as ambient temperature, which vary diurnally and seasonally. It is not yet clear how plants sense temperature and integrate this information into their development. We have previously shown that H2A.Z-nucleosomes are evicted in response to warmer temperatures. It is not clear however, whether the link between transcriptional responsiveness and changes in H2A.Z binding in context of temperature shifts is a global trend that can be seen throughout the genome, or the phenomenon is specific to a specialised set of temperature-responsive genes. In addition to the role of H2A.Z-nucleosome dynamics in the transcriptional response to temperature, it was shown that genes strongly misregulated in the h2a.z mutant are enriched for gene categories involved in response to multiple environmental cues. This suggests that H2A.Z could be implicated in the transcriptional response to various environmental inputs, raising the question: What brings the specificity of H2A.Z dynamics in response to temperature? To address this question we have profiled H2A.Z-nucleosome occupancy genome wide (using ChIP-seq) during a time course after temperature variation and compared its dynamics to transcriptional changes. We identified a fast, targeted and transient eviction of H2A.Z associated with transcriptional activation in response to temperature for a few hundreds genes. This eviction is associated with a reduction of the stability of the nucleosome. Moreover the genes with a fast H2A.Z eviction were strongly enriched in heat shock elements in their promoter and we observed a strong association between HSF1 binding and H2AZ eviction at warm temperature. These results highlight the importance of the interplay between transcription factors and chromatin to allow a controlled and dynamics response to temperature. Overall design: RNA-seq were generated in duplicate for seedlings shifted to warm temperature
Publication Title
Transcriptional Regulation of the Ambient Temperature Response by H2A.Z Nucleosomes and HSF1 Transcription Factors in Arabidopsis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Comparison of gene expression profiles of the GL261 cell line (a murine glioma model) grown in duplicate in two different types of media. AC samples where grown in DMEM supplemented by 20% FBS, 5 U/ml pen/strep and 4 mM L-glutamine. NS samples were grown in DMEM/F12 (50/50) supplemented with 2 U/ml pen/strep, 1 ug/ml fungizone, 1x B27, 20 ng/ml bFGF, 20 ng/ml EGF, 20 ng/ml LIF and 5 ug/ml heparin. We have reason to believe the NS media enhances cell de-differentiation.
Publication Title
Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFß1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties (EP) of the cardiomyocytes compared to co-culture with dermal fibroblasts (DFs). The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration. Overall design: We performed RNA-seq for hPSC-CFs, primary CFs and DFs to compare the gene expression for each type of fibroblasts. We also added the hPSC-CMs and hPSCs as the positive and negativ controls in the RNA-seq to compare the gene expression for cardaic factors. Five cell types (hPSC-CFs, human adult CFs and DFs, hPSC-CMs and hPSCs) with 2 biological replicates for each cell type of a total 10 samples were sequenced.
Publication Title
Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors.
Sample Metadata Fields
Specimen part, Subject
View Samples