Filters
Technology
Platform
SRP189661
Mus musculus
62 Downloadable Samples
Illumina HiSeq 4000
Description
While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less understood. By dissecting border regions and combining single-cell RNA sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny and subsets displayed distinct self-renewal capacities upon depletion and repopulation. Single-cell and fate-mapping analysis both suggested there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in the healthy and diseased brain. Overall design: sample of WT choroid plexus, sample of WT dura mater, sample of WT enriched SDM, sample of WT whole brain, sample of 9 months old APP/PS1 mice, sample of 16 months old APP/PS1 mice, sample of 16 months old WT mice, sample of Irf8 KO whole brain, sample of Irf8 KO choroid plexus, sample of Irf8 WT whole brain, sample of Irf8 WT choroid plexus, sample of dura mater with standard protocol and with ActD protocol, sample of choroid plexus with standard protocol and ActD protocol.
Publication Title
A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 23 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
Publication Title
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
Publication Title
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Examine the possible pro-inflammatory gene effects of alloantibody and complement on endothelial cells
Publication Title
Alloantibody and complement promote T cell-mediated cardiac allograft vasculopathy through noncanonical nuclear factor-κB signaling in endothelial cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st), Illumina Genome Analyzer
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina Genome Analyzer, Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Estrogen receptor (ER) is a key regulator of breast growth and breast cancer development. However, the role of ER in metabolic reprogramming, a hallmark of cancer, is not well documented. In this study, using an integrated approach combining genome-wide mapping of chromatin bound ER with estrogen induced transcript and metabolic profiling, we demonstrate that ER reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline metabolism. We show, for the first time, that the ER target gene choline phosphotransferase 1 (CHPT1) plays an essential role in estrogen induced increases in phosphatidylcholine (PtdCho) levels and that CHPT1 promotes tumorigenesis and proliferation. Furthermore, we show that CHPT1 is overexpressed in tumors compared to normal breast. We also demonstrate that ER promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ER for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ER target CHPT1 in breast cancer supports its potential as a therapeutic target.
Publication Title
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The contribution of aberrant DNA methylation and the downstream effects in tumorogenesis through silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations can be reversed, we investigated the effects of the epigenetic therapy in breast cancer cell lines.
Publication Title
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
High-grade gliomas are amongst the most deadly human tumors. Treatment results are overall disappointing. Nevertheless, in several trials around 20% of patients respond to therapy. Diagnostic strategies to identify those patients that will ultimately profit from a specific targeted therapy are urgently needed. Gene expression profiling of untreated tumors is a well established approach for identifying biomarkers or diagnostic signatures. However, reliable signatures predicting treatment response in gliomas do not exist. Here we suggest a novel strategy for developing diagnostic signatures. We postulate that predictive gene expression patterns emerge only after tumor cells have been treated with the agent in vitro. Moreover, we postulate that enriching specimens for tumor initiating cells sharpens predictive expression patterns. Here, we report on the prediction of treatment response of cancer cells in vitro. As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated but not from untreated glioma cells allowed to predict therapy-induced impairment of proliferation of glioma cells in vitro. Prediction can be achieved with as little as 6 genes allowing for a straightforward translation into the clinic once the predictive power of the signature is shown also in vivo. Our strategy of using expression profiles from in vitro treated BTIC-enriched cultures opens new ways for trial design for patients with malignant gliomas.
Publication Title
Response-predictive gene expression profiling of glioma progenitor cells in vitro.
Sample Metadata Fields
Specimen part, Treatment
View Samples