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Mus musculus
55 Downloadable Samples
Illumina HiSeq 3000
Description
The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS) including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. By combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifted towards clonal expansion. Finally, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain's innate immune system. Overall design: CD45+ cells isolated from different CNS compartments (including leptomeninges, perivascular space and parenchyma, and choroid plexus) and Ly6Chigh and Ly6Clow monocytes from blood were FACS-sorted in 384-well plates and used for scRNAseq. All myeloid cells were sorted from C57BL/6N mice with 8-10 weeks of age at naive stage or at different stages of Experimental Autoimmune Encephalomyelitis (preclinical, onset and peak of the disease). Data are representative of 16-18 mice from three independent experiments. mCEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016, Herman et al. 2018).
Publication Title
Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Cell line, Subject
View Samples- Mus musculus
- 543 Downloadable Samples
- Illumina HiSeq 2000
Description
Single cell sequencing of microglia and perivascular macrophages was performed on brain tissue from different brain regions to obtain single cell expression profiles dependent on celltype and regional location. Overall design: 425 cells from mouse (CD-1) brains at different postnatal ages as well as embryonic day E11.5-E18.5.
Publication Title
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Illumina HiSeq 3000
Description
Microglia play critical roles in neural development and homeostasis. They are also implicated in neurodegenerative and neuroinflammatory diseases of the central nervous system (CNS). However, little is known about the presence of spatially and temporally restricted subclasses of microglia during CNS development and disease. Here, we combined massively parallel single-cell analysis, single-molecule FISH, advanced immunohistochemistry and computational modelling to comprehensively characterize novel microglia subclasses, which were transcriptionally different from perivascular macrophages, in up to six different CNS regions during development and diseases. Single-cell analysis revealed specific time- and region-dependent microglia subtypes during homeostasis. In contrast, demyelinating and neurodegenerative diseases evoked context-dependent microglia subtypes with distinct molecular hallmarks and diverse cellular kinetics. Finally, diverse microglia subsets were also identified in normal and diseased human brains. Our data provide new insights into the CNS endogenous immune system during development, health and perturbations. Overall design: CD45+ cells isolated from healthy and MS-affected human brains were FACS-sorted in 384-well plates and used for scRNAseq. The patients were aged between 22 and 25 years. Data comprises 5 healthy and 5 MS patients. CEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016).
Publication Title
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regulation of the cell cycle is intimately linked to erythroid differentiation, yet how these processes are coupled is not well understood. To gain insight into this coordinate regulation, we examined the role that the retinoblastoma protein (Rb), a central regulator of the cell cycle, plays in erythropoiesis. We found that Rb serves a cell-intrinsic role and its absence causes ineffective erythropoiesis, with a differentiation block at the transition from early to late erythroblasts. Unexpectedly, in addition to a failure to properly exit the cell cycle, mitochondrial biogenesis fails to be upregulated concomitantly, contributing to this differentiation block. The link between erythropoiesis and mitochondrial function was validated by inhibition of mitochondrial biogenesis. Erythropoiesis in the absence of Rb resembles the human myelodysplastic syndromes, where defects in cell cycle regulation and mitochondrial function frequently occur. Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation.
Publication Title
Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis.
Sample Metadata Fields
No sample metadata fields
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GSE10567- Macaca mulatta
- 4 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Salmonella enterica serotype Typhimurium cause a localized enteric infection in immunocompetent patients while human immunodeficiency virus (HIV)-infected patients develop a life threatening bacteremia. We used a rhesus macaque ileal loop model to study how simian immunodeficiency virus (SIV) infection triggers defects in mucosal barrier function that enhance S. Typhimurium dissemination. SIV infection resulted in significant depletion of CD4+ T cells in the intestinal mucosa. Gene expression profiling revealed a defective TH17 response (with suppression of IL-17 and IL-22 expression) and impaired homeostasis of the intestinal epithelium in SIV-infected animals during NTS infection. These findings correlated with an impaired ability of lamina propria CD4+ T cells from SIV-infected macaques to produce IL-17 upon ex vivo stimulation, while production of IFN-gamma was not affected. This cytokine imbalance in SIV-infected animals was associated with reduced expression of genes required for intestinal epithelial maintenance and repair, increased fluid secretion during NTS infection, epithelial damage and translocation of a non-invasive S. Typhimurium mutant. Although no defects in neutrophil recruitment were noted, the ileum of SIV-infected animals contained lower levels of the enzyme myeloperoxidase, which may indicate defects in neutrophil killing capacity. S. Typhimurium was recovered in markedly increased numbers from the mesenteric lymph nodes of SIV-infected macaques, illustrating the increased potential for systemic dissemination during co-infection. Our data suggest that SIV-infection causes a multi-factorial defect in mucosal barrier function that promotes bacterial dissemination.
Publication Title
Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Retinoic acid (RA) triggers physiological processes by activating heterodimeric transcription factors comprising retinoic acid (RARa,b,g) and retinoid X (RXRa,b,g) receptors. How a single signal induces highly complex temporally controlled networks that ultimately orchestrate physiological processes is unclear. Using an RA-inducible differentiation model we defined the temporal changes in the genome-wide binding patterns of RARg and RXRa and correlated them with transcription regulation. Unexpectedly, both receptors displayed a highly dynamic binding, with different RXRa heterodimers targeting identical loci. Comparison of RARg and RXRa co-binding at RA-regulated genes identified putative RXRa-RARg target genes that were validated with subtype-selective agonists. Gene regulatory decisions during differentiation were inferred from transcription factor target gene information and temporal gene expression. This analysis revealed 6 distinct co-expression paths of which RXRa-RARg is associated with transcription activation, while Sox2 and Egr1 were predicted to regulate repression. Finally, RXRa-RARg regulatory networks were reconstructed through integration of functional co-citations. Our analysis provides a dynamic view of RA signalling during cell differentiation, reveals RA heterodimer dynamics and promiscuity, and predicts decisions that diversify the RA signal into distinct gene-regulatory programs.
Publication Title
Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In vivo reprogramming drives Kras-induced cancer development.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Macaca mulatta
- 12 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
We used microarrays to detail the global gene expression changes in the ileum of SIV-infected and uninfected macaques following administration of L. plantarum.
Publication Title
PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host-microbe intersection during SIV infection.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Accumulation of genetic mutations is thought to be a primary cause of cancer. However, a set of genetic mutations sufficient for cancer development remains unclear in most cancers, including pancreatic cancer. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We first demonstrate that Kras and p53 mutations are insufficient to induce activation of ERK signaling and cancer development in the pancreas. We next show that short transient expression of reprogramming factors (1-3 days) in pancreatic acinar cells results in repression of acinar cell enhancers and reversible loss of acinar cell properties. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce robust and persistent activation of ERK signaling in acinar cells and rapid formation of pancreatic ductal adenocarcinoma (PDAC). In contrast, forced expression of acinar cell-related transcription factors inhibits pancreatitis-induced activation of ERK signaling and development of precancerous lesions in Kras-mutated acinar cells.
Publication Title
In vivo reprogramming drives Kras-induced cancer development.
Sample Metadata Fields
Sex, Specimen part
View Samples