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SRP095117
Mus musculus
8 Downloadable Samples
NextSeq 500
Description
In Multiple Sclerosis, the pathological interaction of autoreactive helper T (TH) cells with mononuclear phagocytes in the central nervous system (CNS) drives initiation and maintenance of chronic neuroinflammation. Herein, we found that intrathecal transplantation of neural stem cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived dendritic cells (moDCs) in the CNS leading to improved clinical outcome. NPCs treatment reduced in the CNS IL-23, IL-1 and TNF-a, cytokines required for terminal differentiation of TH cells and accordingly GM-CSF-producing pathogenic TH cells. In vivo and in vitro transcriptome analyses disclosed that NPC secreted factors induce an inhibition of DC differentiation and maturation, favoring a fate switch towards an anti-inflammatory phenotype. We identified TGF-ß2 as the crucial mediator of NPC immunomodulation: TGFß2 knockout NPCs transplanted in EAE are ineffective in impairing moDC accumulation within the CNS and fail to drive clinical improvement. This study provides evidence that intrathecally injected NPCs interfere with CNS-compartmentalized inflammation of the effector phase of EAE, reprogramming, through the secretion of TGF-ß2, inflammatory monocyte-derived DCs towards anti-inflammatory myeloid cells. Overall design: mRNA profiles of monocyte derived-dendritic cells (moDCs) isolated by FACS sorting at 7 days post-treatment from the CNS (hindbrain and spinal cord) of quadruplicate pool of 4–7 MOG35-55-immunized C57Bl/6 mice either intrathecally injected with PBS or 1 million neural precursor cells (NPCs) at the peak of the disease (2-4 days after clinical onset).
Publication Title
Neural precursor cell-secreted TGF-β2 redirects inflammatory monocyte-derived cells in CNS autoimmunity.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Reprogramming resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward towards the possibility of treating brain injuries or diseases. Here, we show that neurons reprogrammed using Ascl1, Lmx1a and Nurr1 functionally mature and integrate into existing brain circuitry, and that the majority of the reprogrammed neurons have properties of fast spiking, parvalbumin-containing interneurons. Overall design: A total of 6 samples were analyzed. Each sample is consists of approximately 33 laser-captured reprogrammed-neurons identified by nuclear GFP and expressing the transcription factors Ascl1, Lmx1a and Nurr1 (ALN).
Publication Title
Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 229 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
One of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms.
Publication Title
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The cytotoxic drug edelfosine is a synthetic analog of 2-lysophosphatidylcholine. Edelfosine is incorporated by highly proliferating cells, e.g. activated immune cells. It is unknown if the described mechanisms for edelfosine action attained by in vitro approaches exclusively contribute to the observed EAE-amelioration or if edelfosine may exert additional, probably more general and possibly immunoablative effects within the setting of autoimmunity.
Publication Title
The orally available, synthetic ether lipid edelfosine inhibits T cell proliferation and induces a type I interferon response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
C3H10T1/2 stem cells are committed to the adipocyte lineage by treatment with BMP-4 and grown to postconfluence. When subjected to our standard differentiation protocol, the committed cells differentiate into adipocytes in a manner indistinguishable from that of 3T3-L1 preadipocytes. In contrast, C3H10T1/2 cells not committed with BMP-4 remain undifferentiated despite treatment with differentiation inducers. The molecular basis of the commitment process, however, has not been elucidated. Since postconfluent uncommitted and committed C3H10T1/2 cells respond differently to the differentiation inducers, it was reasoned that the two cell types differed at the gene expression level. Therefore, we undertook microarray gene expression profiling to detect changes between the two cell populations at postconfluence to identify expressed genes that may be responsible for the dramatic change in phenotype.
Publication Title
BMP-4 treatment of C3H10T1/2 stem cells blocks expression of MMP-3 and MMP-13.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells.
Sample Metadata Fields
Cell line
View Samples- Danio rerio
- 11 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Amputation of heart tissue followed by regeneration of the heart. Samples were taken at 0 hpa (hours post-amputation), 6 hpa, 12 hpa, 24 hpa, 3 dpa and 5 dpa.
Publication Title
Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The function of cell-cell contact for radiochemosensitivity is unclear. Here, we investigate the role of the E-cadherin/catenin complex proteins under more physiological three-dimensional (3D) cell culture conditions in a panel of CRC cell lines.
Publication Title
Differential effects of α-catenin on the invasion and radiochemosensitivity of human colorectal cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 128 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pancreatic islets are central in type 2-diabetes development, which coincides with increased activity of innate immunity. Intriguingly, human pancreatic islets express many complement genes. The most highly expressed gene was the complement inhibitor CD59 that is GPI anchored to the cell membrane, which unexpectedly was found in high amounts intracellularly in beta cells. Silencing of CD59 strongly suppressed insulin secretion. Importantly, this suppression was unrelated to established CD59 functions, but rather depletion of intracellular CD59. Imaging experiments identified a distal site of inhibition in the exocytotic pathway, but prior to emptying of the insulin granules. Proximity Ligation Assays pin-pointed the mechanism to impaired turnover of exocytosis-regulating SNARE-proteins and CD59 was detected in complex with VAMP2 and syntaxin. CD59 was downregulated by 24-h glucose incubations in human islets, rat cell lines and in islets from three rodent diabetes models.
Publication Title
The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TCF7L2 is a master regulator of insulin production and processing.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples