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GSE5078
Mus musculus
23 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze.
Publication Title
Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
Sample Metadata Fields
Sex, Age, 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
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A suggested role for fibrillr collagen topology in the pregnancy-induced protection and invasive phenotype.
Publication Title
Collagen architecture in pregnancy-induced protection from breast cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 36 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs.
Publication Title
Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs.
Publication Title
Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Skin conventional dendritic cells (cDC) exist as two distinct subsets, cDC1 and cDC2, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here we examined the roles of dermal cDC1 and cDC2 during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1, but not cDC2, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine VEGFa by a minor subset of activated EpCAM+CD59+Ly6D+ cDC1. Neutrophil recruitment by dermal cDC1 was also observed during S. aureus, BCG or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1 are essential regulators of the innate response in cutaneous immunity, with roles beyond classical antigen presentation. Overall design: Examined the effect of cDC1 (CD103+DC) depletion on neutrophils infiltrating the skin during P. acnes infection.
Publication Title
A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2000
Description
Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation and in multiple pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within tissue parenchyma remain poorly defined. Here, we studied IMs from murine lung, fat, heart and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localisation. Using a mouse model of inducible macrophage depletion (SLCO2B1-DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs exist across tissues and exhibit conserved niche-dependent functional programming. Overall design: Mouse Lung Interstitial Macrophages single cell mRNA profiles
Publication Title
Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches.
Sample Metadata Fields
Specimen part, Subject
View Samples