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SRP091455
Mus musculus
10 Downloadable Samples
Illumina HiSeq 2500
Description
Hunger, driven by negative energy balance, elicits the search for and consumption of food. In mammals, this is orchestrated principally through the activity of neurons in the hypothalamus, direct manipulation of which can potently drive food intake. However, the neural circuits outside of the hypothalamus that control feeding are poorly understood. Here, we identify two functionally opponent cell types within the dorsal raphe nucleus (DRN), marked by the vesicular transporters for GABA (Vgat) or glutamate (VGLUT3), that project to many known feeding centers and rapidly control feeding. We find that DRNVgat neurons drive, while DRNVGLUT3 neurons suppress, food intake. Furthermore, through the development and application of cell type-specific molecular profiling technologies, we identify many differentially expressed transmembrane receptors, which may represent unique druggable targets. Local application of agonists for these receptors potently modulates feeding, recapitulating the effects of cell-specific manipulations. Together, these data establish a key role for the DRN in controlling food intake and add an important anatomic site that controls energy balance. Overall design: Paired - Inputs and IPs; Unpaired for Vgat/VGLUT3 comparison
Publication Title
Identification of a Brainstem Circuit Controlling Feeding.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
A neuronal PI(3,4,5)P3-dependent program of oligodendrocyte precursor recruitment and myelination was identified in mice that conditionally lack PTEN in cerebellar granular cells (PTEN cKO)
Publication Title
A neuronal PI(3,4,5)P<sub>3</sub>-dependent program of oligodendrocyte precursor recruitment and myelination.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We describe here a male infant with a 100 kb de novo Xq28 deletion encompassing parts of the TMEM187 and MECP2 protein-coding genes and the IRAK1 protein-coding gene, as well as the MIR3202-1, MIR3202-2, and MIR718 RNA-coding genes. We analyzed the impact of human IRAK-1 deficiency on a genome-wide gene expression in human fibroblasts in response to TLR2/6, TLR4 agonists as well as to IL-1 and TNF-, using primary fibroblasts from healthy controls and IRAK-4-, MyD88- and MECP2-deficient patients for comparison.
Publication Title
Inherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Blood-stage malaria initiates both innate and adaptive immune responses, inclusive a strong activation of the mononuclear phagocyte network. Here we show that Plasmodium infection results in a transient loss of embryonically established tissue-resident macrophages in spleen, liver and lungs, much before the peak of parasitemia. During acute blood-stage malaria, fate mapping analysis revealed that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche mainly through self-renewal. Interestingly, the local microenvironment of spleen and liver can “imprint” the molecular characteristics of fetal-derived macrophages in new immigrants from bone marrow including almost identical gene expression profiles and turnover kinetics. Overall design: Mice were infected with parasitized P. yoelii erythrocytes. Organ samples were collected in triplicates from uninfected mice and from mice infected 35 days before and after parasite clearance.
Publication Title
Organ-Specific Fate, Recruitment, and Refilling Dynamics of Tissue-Resident Macrophages during Blood-Stage Malaria.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Platelet reactivity (PR) in cardiovascular (CV) patients is variable between individuals and modulates clinical outcome. However, the determinants of platelet reactivity are largely unknown. Integration of data derived from high-throughput omics technologies may yield novel insights into the molecular mechanisms that govern platelet reactivity. The aim of this study was to identify candidate genes modulating platelet reactivity in aspirin-treated cardiovascular patients PR was assessed in 110 CV patients treated with aspirin 100mg/d by aggregometry using several agonists. 12 CV patients with extreme high or low PR were selected for transcriptomics, proteomics and miRNA analysis.
Publication Title
New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 222 Downloadable Samples
- IlluminaHiSeq2000
Description
Dendritic cells (DCs) are antigen sensing and presenting cells that are essential for effective immunity. Existing as a multi-subset population, divided by distinct developmental and functional characteristics1,2, DC subsets play important and unique roles in responses to pathogens, vaccines and cancer therapies, as well as during immune-pathologies. Therefore therapeutic manipulation of the DC compartment is an attractive strategy. However, our incomplete knowledge of the inter-relationship between DC subsets and how they develop from progenitors in the bone marrow (BM) has so far limited the realization of their therapeutic potential. DCs arise from a cascade of progenitors that gradually differentiate in the BM; first, the macrophage DC progenitor (MDP), then common DC progenitor (CDP), and lastly the Pre-DC, which will leave the BM to seed peripheral tissues before differentiating into mature DCs3,4. While the basic outline of this process is known, how subset commitment and development is regulated at the molecular level remains poorly understood. Here we reveal that the Pre-DC population in mice is heterogeneous, containing uncommitted Ly6c+/-Siglec-H+ cells as well as Ly6c+Siglec-H- and Ly6c-Siglec-H- sub-populations that are developmentally fated to become Th2/17-inducing CD11b+ DCs and Th1-inducing CD8a+ DCs, respectively. Using single cell analysis by microfluidic RNA sequencing, we found that DC subset imprinting occurred at the mRNA level from the CDP stage, revealing that subset fate is defined in the BM and not in peripheral tissues. Single cell transcriptome analysis allowed identification of the molecular checkpoints between progenitor stages and revealed new regulators of DC-poiesis, shedding light on the role of cell cycle control and specific transcription factors in DC lineage development. These data advance our knowledge of the steady-state regulation of DC populations and open promising new avenues for investigation of the therapeutic potential of DC subset-specific targeting in vivo to improve vaccine-based and immunotherapeutic strategies. Overall design: Single cell mRNA sequencing was used to investigate the transcriptomic relationships within the Dendritic cell precursor compartment within the BM as well as between single Dendritic cell precursors
Publication Title
Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Dendritic cells (DCs) are antigen sensing and presenting cells that are essential for effective immunity. Existing as a multi-subset population, divided by distinct developmental and functional characteristics1,2, DC subsets play important and unique roles in responses to pathogens, vaccines and cancer therapies, as well as during immune-pathologies. Therefore therapeutic manipulation of the DC compartment is an attractive strategy. However, our incomplete knowledge of the inter-relationship between DC subsets and how they develop from progenitors in the bone marrow (BM) has so far limited the realization of their therapeutic potential. DCs arise from a cascade of progenitors that gradually differentiate in the BM; first, the macrophage DC progenitor (MDP), then common DC progenitor (CDP), and lastly the Pre-DC, which will leave the BM to seed peripheral tissues before differentiating into mature DCs3,4. While the basic outline of this process is known, how subset commitment and development is regulated at the molecular level remains poorly understood. Here we reveal that the Pre-DC population in mice is heterogeneous, containing uncommitted Ly6c+/-Siglec-H+ cells as well as Ly6c+Siglec-H- and Ly6c-Siglec-H- sub-populations that are developmentally fated to become Th2/17-inducing CD11b+ DCs and Th1-inducing CD8+ DCs, respectively. Using single cell analysis by microfluidic RNA sequencing, we found that DC subset imprinting occurred at the mRNA level from the CDP stage, revealing that subset fate is defined in the BM and not in peripheral tissues. Single cell transcriptome analysis allowed identification of the molecular checkpoints between progenitor stages and revealed new regulators of DC-poiesis, shedding light on the role of cell cycle control and specific transcription factors in DC lineage development. These data advance our knowledge of the steady-state regulation of DC populations and open promising new avenues for investigation of the therapeutic potential of DC subset-specific targeting in vivo to improve vaccine-based and immunotherapeutic strategies.
Publication Title
Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process, and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative datasets that can be leveraged to explore post-transcriptional and post-translational processes that are essential for mitochondrial adaptation.
Publication Title
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples