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GSE60783
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
- 24 Downloadable Samples
- Illumina HiSeq 1500
Description
Here we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases. Overall design: Examination of GMPs in six different conditions by RNA-seq
Publication Title
Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 1500
Description
Here we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced systemic inflammation, which was undectable in serum soon after mice were shifted back to chow diet (CD). In contrast, myeloid cell responses towards innate stimuli remained broadly augmented. WD induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells, leading to increased proliferation as well as enhanced innate immune and interferon responses towards in vivo LPS challenge. QTL analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with LPS suggested inflammasome-mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/--deficient mice lacked WD-induced systemic inflammation or myeloid progenitor proliferation and reprogramming. Hence, NLRP3 mediates trained immunity following WD and could thereby arbitrate the potentially deleterious effects of trained immunity in inflammatory diseases. Overall design: Examination of GMPs in six different conditions by RNA-seq
Publication Title
Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 28 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
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Microarray analysis of murine microglia from different stages of development was performed. Results showed that different phases of microglia development had different group of genes up-regulated for specific functions.
Publication Title
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2500
Description
RNAseq was performed on microglia from male and female, SPF or GF mice to elucidate the genetic differences implicated by microbiota and gender. DEGs between the various groups gave some ideas on what different pathways or functions might be affected due to the different factors. Overall design: Microglia from SPF and GF mice from embryonic and adult stages of both gender were sorted for sequencing. DEGs were obtained to observe if any signicant genes were affected. Pathway analysis was performed with the set of DEGs.
Publication Title
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- NextSeq 500
Description
Within the bone marrow, hematopoietic stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with the in vivo potential or gene regulatory mechanisms. Here we comprehensively identify myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups showing unexpected transcriptional priming towards seven differentiation fates, but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting the process is tightly regulated. Histone maps and knockout assays are consistent with the transcriptional states while traditional transplantation experiments are only partially overlapping myeloid transcriptional priming. Our analyses uncover the function of the underlying regulatory mechanisms for several sub groups and establishes a general framework for dissecting hematopoiesis. Overall design: Bone marrow Lin- cKit+ Sca1- myeloid progenitors mRNA profiles from single cells were generated by deep sequencing of thousands of single cells, sequenced in several batches in an Illumina NextSeq Please note that [1] raw data files were processed as single-ended file since second read (mate) files contain only cell/molecule barcodes and therefore, not provided. This information was appended to the fastq entry header [2] The ''experimental_design.txt'' file explains the correspondence of each single cell (WXXXX) in the ''umitab.txt'' to a sample (ABXXXX).
Publication Title
Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part, Subject
View Samples