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GSE66766
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Branched-chain amino acids (BCAA) have emerged as predictors of type 2 diabetes (T2D). However, their potential role in the pathogenesis of insulin resistance and T2D remains unclear. By integrating data from skeletal muscle gene expression and metabolomic analyses, we demonstrate evidence for perturbation in BCAA metabolism and fatty acid oxidation in skeletal muscle from insulin-resistant humans. Experimental modulation of BCAA flux in cultured cells alters fatty acid oxidation in parallel. Furthermore, heterozygosity for the BCAA metabolic enzyme methylmalonyl-CoA mutase (MUT) alters muscle lipid metabolism in vivo, resulting in increased muscle triacylglycerol (TAG) accumulation and increased body weight after high-fat feeding. Together, our results demonstrate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by reducing fatty acid oxidation and increasing TAG accumulation.
Publication Title
Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dent disease has multiple defects attributed to proximal tubule malfunction including low molecular weight proteinuria, aminoaciduria, phosphaturia and glycosuria. In order to understand the changes in kidney function of the Clc5 transporter gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal tubules of mouse kidneys.
Publication Title
Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion between pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem and progenitor cells (HSPCs), and mature hematopoietic cells. Quantification of chromatin composition by high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSPCs, with a further reduction in euchromatin as HSPCs transition into mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9a resulted in delayed hematopoietic stem cell (HSC) differentiation. Our results demonstrate significant global rearrangements of chromatin structure during embryonic and adult stem cell differentiation, and that heterochromatin formation by H3K9 methylation is an important regulator of HSC differentiation. Overall design: Examination of gene expression profile of in vitro cultured mouse HSC with the G9a inhibitor UNC0638
Publication Title
Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 4000
Description
To ask whether MANF contributes to the rejuvenating effects of heterochronic parabiosis, we generated heterochronic pairs in which 20 month old WT mice were combined with either 4 month old MANFHet (O-YgHet) or WT (O-YgWT) littermates, and maintained for 5 weeks before analysis. Control pairs in which old WT mice were combined together (O-O) were used. Livers were collected from each animal in the pair and RNA was sequenced for 5 independent animals/condition. Overall design: RNA was extracted and sequenced for 5 animals/condition
Publication Title
MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage.
Sample Metadata Fields
Age, Subject
View Samples- Homo sapiens
- 88 Downloadable Samples
- Illumina HiSeq 2500
Description
Infiltrating T-lymphocytes from the peripheral blood into the central nervous system (CNS) play a dynamic role in the development of a neurological immune-mediated diseases. HAM/TSP is a chronic progressive inflammatory neurological disorder associated with human T-cell lymphotropic virus type I (HTLV-I) infection. In this chronic myelopathy, virus-infected circulating T-cells infiltrate the CNS and an immune response is initiated against the components of CNS. As the HTLV-I proviral load (PVL) has been used as the best clinical marker for patient diagnostic with HAM/TSP, we hypothesized there might be a signature on T-cell receptor (TCR) clonal repertoire in these patients, which could distinguish HAM/TSP patients from the healthy population, as well as from patients with a more heterogeneous CNS-reactive inflammatory disease as multiple sclerosis (MS). With this in mind, we applied an innovative unbiased molecular technique – unique molecular identifier (UMI) library-strategy to investigate with high accuracy the TCR clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR ß-chain libraries were sequenced from 2 million peripheral mononuclear cells (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). To address whether the clonal expansion correlates with the patient's PVL level, analysis of longitudinal TCR repertoire was performed in 2 HAM/TSP patients. Over 5.6 million TCR sequences were generated per sample on HiSeq 2500 Illumina system and analyzed through the molecular identifier groups-based error correction pipeline (MiGEC). Bioinformatic analysis showed that clones with more than 8 reads had a lower coefficient of variation (CV) and then could be used with confidence to evaluate the TCR clonal expansion. While HAM/TSP patients showed the higher clonal T-cell expansion compared to MS and HC, increase of the TCR clonal expansion was inversely correlated with the diversity of TCR repertoire in all subject's group. In addition, correlation of the PVL with TCR clonal expansion was observed in HAM/TSP patients at longitudinal time-points. Surprisingly, MS patients showed a higher diversity of TCR repertoire along with a very slight clonal T-cell expansion in comparison to either HAM/TSP patients or HC. Despite of the higher TCR clonal expansion in HAM/TSP patients, a non-shared or “private” TCR repertoire was observed in these patients. No clones that shared the same CDR3 amino acid sequences were seen in HC and MS patients. However, a cluster of related CDR3 amino acid sequences were observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. It suggestes that a TCR-repertoire signature might characterize patients with MS. Our findings suggest that even though a unique TCR-b repertoire shapes the immune response in patients with neurological immune-mediated disease, a relatedness on clonal T-cell repertoire exist in MS. Overall design: TCR-ß profiles for 68 human samples were generated via deep sequencing using the Illumina HiSeq 2500 system and reagents. Of those profiled, 20 were not diagnosed as having HAM/TSP or MS (i.e., Healthy Control, "HC"), 14 were diagnosied as having HAM/TSP, and 34 were diagnosed as having MS.
Publication Title
Comprehensive Analysis of TCR-β Repertoire in Patients with Neurological Immune-mediated Disorders.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Race, Subject
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of meningiomas) and the gene expression profiles could help to explain the differences in clinical behaviour of meningiomas.
Publication Title
Gene expression profiles of meningiomas are associated with tumor cytogenetics and patient outcome.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
CD141+DNGR-1+ cDC1 have a dual origin. Both MLP and CMP can differentiate in CD141+DNGR-1+ cDC1s.
Publication Title
Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
GM-CSF derived bone marrow cultures contain several subsets of CD11c+MHCII+ mononuclear phagocytes
Publication Title
GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c(+)MHCII(+) Macrophages and Dendritic Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 305 Downloadable Samples
- IlluminaHiSeq2500, NextSeq500
Description
Hematopoietic stem cell (HSC) transplantation has the potential to cure blood disorders but is limited by donor availability. Hence innovative approaches to engineer HSC are critically needed. HoxB4 over-expression in mouse embryonic stem cell-derived HSC (ESC-HSC) confers long-term engraftment, yet lacks efficient lymphogenesis. Transcriptome comparison of ESC-HSC versus embryo-derived HSC showed that ESC-HSC are deficient in expression programs activated by Notch. Therefore, we aim to improve ESC-HSC by further providing Notch signals through Notch1 intra-cellular domain transgene activation or by ligand stimulation. Here, we report that Notch-enhanced ESC-HSC (nESC-HSC) confer clonal multipotentiality with robust lymphopoiesis that endows adaptive immunity. Notably, nESC-HSC further evolve to a hybrid cell-type co-expressing gene regulatory networks of hematopoietic stem/progenitor cells and differentiated lineages at single-cell level that accounts for multipotentiality. Our work reveals a proof-of-concept model of HSC engineering by assembling self-renewing factor and lineage-guiding pathway into one product-cell that functionally recapitulate HSC in vivo. Overall design: The gene expression of murine hematopoietic stem cells, ESC, and HSC-like cells derived from differentiation of embryonic stem cells and subsequently transplanted were determined by single cell RNA-Seq.
Publication Title
Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity.
Sample Metadata Fields
No sample metadata fields
View Samples