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GSE27280
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Publication Title
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Sample Metadata Fields
Specimen part
View Samples- Escherichia coli, Bifidobacterium longum
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
"Omics" technologies have been developed to understand the whole complex microbial systems; however, most omics studies reported so far were utilized to analyze the living matters of single-species. To understand the cell-cell interaction in the gut microbial complex, we selected to examine the interaction of Escherichia coli O157:H7 (O157) and Bifidobacterium longum (BL), known as a pathogenic and a commensal bacteria, as a first step for understanding the whole gut microbial complex. We have developed a novel time-lapse 2D-NMR metabolic profiling system in order to measure the extracellular metabolites, which are considered a key factor to understand the bacterial crosstalk. Furthermore, in combination with transcriptome and proteome analysis, we found that the relationship between BL and O157 could be partially regarded as the producer and the consumer of nutrients, especially in the case of serine and aspartate metabolism. These findings suggest that our novel profiling systems could be a powerful tool toward understanding crosstalk of the whole microbial complex such as the gut, industrial bioreactors or environmental microbial communities.
Publication Title
Dynamic omics approach identifies nutrition-mediated microbial interactions.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology, a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification.
Publication Title
Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosomelike acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies.
Publication Title
LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The effect Ds insertion mutation in Ds13-2198-1 line on the gene expression profiles was investigated. The genes for photosynthesis and some transcriptional factors were upregulated while genes for metabolism were downregulated.
Publication Title
Top-down phenomics of Arabidopsis thaliana: metabolic profiling by one- and two-dimensional nuclear magnetic resonance spectroscopy and transcriptome analysis of albino mutants.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 35 Downloadable Samples
Illumina HiSeq 2000
Description
The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan. Overall design: RNAsequencing expression profiles of livers and triceps surae hindlimb muscle from 25 week-old Ins1-/-;Ins2+/- and Ins1-/-;Ins2+/+ littermate control mice on one of two different diets (Diet A and B)
Publication Title
Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Purpose: The goal of this study is to compare the transcriptional phenotype of lymphoid and kidney-infiltrating T cell populations in the setting of systemic inflammatory disease to determine how tissue location alters their phenotype. Methods: mRNA profiles of T cells isolated from 23-week-old nephritic (protein score of 3+ on dipstick) mice were used in this study. T cells were isolated by flow cytometry gated on CD45+Thy1.1+CD44+ and either CD4 or CD8+ T cells. RNA was isolated using the RNeasy Plus Micro Kit (Qiagen). Samples were sequenced using Illumina NextSeq 500 with 75bp paired-end reads and aligned to the mm10 genome using the STAR aligner. The number of uniquely aligned reads ranged from 10 to 12 million. Using an optimized data analysis workflow, Gene-level counts were determined using featureCounts and raw counts were analyzed for differential expression using the “voom” method in the “limma” R package. Results: After determining genes that were differentially expressed between splenic T cells and KIT, we performed gene set enrichment analysis (GSEA. Differentially expressed genes were compared to several previously defined gene signatures that are characteristic of CD8+ and CD4+ T cell exhaustion in the chronic LCMV infection model and tumor infiltrating lymphocytes. Genes from the CD8+ exhaustion cluster were significantly enriched among genes that were differentially expressed in CD8+ KITs vs CD8+ splenocytes. Overall design: mRNA profiles of CD4 and CD8 T cells from spleen and kidney of 23 week old wild MRL/lpr mice were generated in triplicate by sequencing using Illumina NextSeq 500
Publication Title
Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Retinal ganglion cells (RGCs) and retinal pigment epithelium (RPE) cells are two retinal cell types that are affected by the most prevalent retinal diseases leading to irreversible blindness, such as glaucoma affecting the former and age-related macular degeneration affecting the latter. One of the most promising approaches for the therapy of these diseases is via the autologous transplantation of RGC or RPE cells derived from the induced pluripotent stem cells (iPSCs). This emphasizes the importance of detailed characterization and understanding of the mechanisms of differentiation of iPSCs into retinal lineages on the genome-wide scale. Such information can be used to identify novel crucial regulators of differentiation, optimisation of differentiation protocols to make them more efficient and safe, identification of novel specific biomarker signatures of differentiated cells. In this study, we performed the genome-wide transcriptome analysis of terminally differentiated RGC and RPE lineages, as well as intermediate retinal progenitor cells (RPCs) of optic vesicles (OVs) derived from the human induced pluripotent stem cells (iPSCs). In our analysis we specifically focused on the classes of transcripts that encode regulators of gene expression, such as transcription factors, epigenetic factors, and components of signaling pathways.
Publication Title
Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Compared the global gene expression profiles of HD- and CON-iPSC-derived neurons
Publication Title
Elucidating the role of the A2A adenosine receptor in neurodegeneration using neurons derived from Huntington's disease iPSCs.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hepatoblastoma (HB) is the most common pediatric liver tumor, and there are no targeted therapies available for children with HB. We have previously developed a murine model of HB which is driven by coactivation of the oncogenes YAP1 and -catenin (CTNNB1) [Tao J, Calvisi D, Ranganathan S, et al. Gastroenterology, 2014 Sep; 147(3): 690701]. We used the Sleeping Beauty transposase system combined with hydrodynamic tail vein injection to deliver plasmids containing mutant activated forms of YAP1 (YAP S127A) and -catenin (N90 -catenin) to a small number of pericentral hepatocytes. We have shown that these few transformed hepatocytes proliferate and dedifferentiate, eventually forming histologically heterogeneous tumors that resemble various subtypes of human HB (which is also highly heterogeneous), including areas of well-differentiated fetal, crowded fetal, embryonal, and blastemal HB. Our goal was to investigate how coactivation of YAP1 and -catenin drive the dedifferentiation of hepatocytes into hepatoblast-like tumor cells over time, leading to HB tumors. In order to measure changes in gene expression during tumorigenesis in our model, we used an Affymetrix microarray to analyze isolated RNA from wild type FVB mouse livers, mouse HB tumor tissue, and non-tumor liver tissue adjacent to HB tumors.
Publication Title
Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma.
Sample Metadata Fields
Age, Specimen part
View Samples