Filters
Technology
Platform
Mus musculus
81 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Recent studies have shown that tissue macrophages (MF) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize the tissues before birth. Further studies have proposed that developmentally distinct tissue MF can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we established an inducible fate mapping system that facilitated the identification of A2 progenitors of the YS as source of F4/80hi but not CD11bhi MF. Large-scale transcriptional profiling of MF precursors from the YS until adulthood allowed the description of a complex MF pedigree. We further identified a distinct molecular signature of F4/80hi and CD11bhi MF and found that Irf8 was vital for MF maturation and the innate immune response. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MF.
Publication Title
Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Host microbiota constantly control maturation and function of microglia in the CNS.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
As tissue macrophages of the central nervous system (CNS), microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. Here we reveal significant contributions of the host microbiota to microglia homeostasis as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulate microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings reveal that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be restored to some extent by complex microbiota.
Publication Title
Host microbiota constantly control maturation and function of microglia in the CNS.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
As tissue macrophages of the central nervous system (CNS), microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. Here we reveal significant contributions of the host microbiota to microglia homeostasis as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulate microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings reveal that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be restored to some extent by complex microbiota.
Publication Title
Host microbiota constantly control maturation and function of microglia in the CNS.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Normal arteries contain a large population of tissue resident macrophages (M). Their origins, as well as the mechanisms that sustain them during homeostasis and disease, however, are poorly understood. Gene expression profiling, we show, identifies arterial M as a distinct population among tissue M. Ontologically, arterial M arise before birth, though CX3CR1-, Csf1r-, and Flt3-driven fate mapping approaches demonstrate M colonization occurs through successive contributions of yolk sac (YS) and conventional hematopoiesis. In adulthood, arterial M renewal is driven by local proliferation rather than monocyte recruitment from the blood. Proliferation sustains M not only during steady state conditions, but mediates their rebound after severe depletion following sepsis. Importantly, the return of arterial M to functional homeostasis after infection is rapid; repopulated M exhibit a transcriptional program similar to resting M and efficiently phagocytose bacteria. Collectively, our data provide a detailed framework for future studies of arterial M function in health and disease.
Publication Title
Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal1. In various pathophysiological conditions, erythrocyte life span is severely compromised, which threatens the organism with anemia and iron toxicity 2,3. Here we identify anon-demand mechanism specific to the liver that clears erythrocytes and recycles iron. We showthat Ly-6Chigh monocytes ingest stressed and senescent erythrocytes, accumulate in the liver, and differentiate to ferroportin 1 (FPN1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1+ Tim-4neg macrophages are transient, reside alongside embryonically-derived Tim-4high Kuppfer cells, and depend on Csf1 and Nrf2. The spleenlikewise recruits iron-loaded Ly-6Chigh monocytes, but they do not differentiate into ironrecycling macrophages due to the suppressive action of Csf2, and are instead shuttled to the livervia coordinated chemotactic cues. Inhibiting this mechanism by preventing monocyte recruitment to the liver leads to kidney failure and liver damage. These observations identify the liver as the primary organ supporting emergency erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity.
Publication Title
On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We generated the transcriptional regulatory footprint of phthalimide neovascular factor 1 (PNF1)a novel synthetic small molecule that exhibits significant in vitro endothelial potency and significant in vivo microvascular network expansionby performing comparative microarray analysis on PNF1-stimulated (versus control) human microvascular endothelial cells (HMVEC) spanning 1-48 h post-supplementation. We subsequently applied network analysis tools (including substantial libraries of information regarding known associations among network components) to elucidate key signaling components and pathways involved in the PNF1 mechanism-of-action. We identified that PNF1 first induces function of the tumor necrosis factor-alpha (TNF-) signaling pathway, which in turn affects transforming growth factor-beta (TGF-) signaling.
Publication Title
Mechanistic exploration of phthalimide neovascular factor 1 using network analysis tools.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
In most embryos, the mid-blastula transition is a complex process featuring maternal RNA degradation, cell cycle pause, zygotic transcriptional activation and morphological changes. The nucleocytoplasmic (N/C) ratio has been proposed to control the multiple events at MBT. To understand the global transcriptional response to the changes of the N/C ratio, we profiled wild type and haploid embryos using cDNA microarrays at three developmental stages.
Publication Title
Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Kaposis sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response.
Publication Title
Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 3 inhibits gamma interferon and major histocompatibility complex class II expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples
GSE5587- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Early Growth Response (Egr) family of transcription factors consists of 4 members (Egr1-4) that are expressed in a wide variety of cell types. A large body of evidence point to a role for Egr transcription factors in growth, survival, and differentiation. A major unanswered question is whether Egr transcription factors serve similar functions in diverse cell types by activating a common set of target genes. Signal transduction cascades in neurons and lymphocytes show striking parallels. Activation of either cell type activates the Ras-MAPK pathway and, in parallel, leads to increases in intracellular calcium stimulating the calcineurin-NFAT pathway. In both cell types, the strength of the activation signal affects the cellular outcomes and very strong stimuli lead to cell death. Notably both these pathways converge on the induction of Egr genes. We believe that downstream targets of Egr transcription factors in lymphocytes may also be activated by Egr factors in activated neurons. There is precedence for common target gene activation in these two cell types: apoptosis in both activated T cells and methamphetamine stimulated neurons occurs via FasL induction by NFAT transcription factors. We propose to use developing T lymphocytes (thymocytes) as a model system for discovery of Egr-dependent target genes for several reasons. First, we have observed a prominent survival defect in thymocytes from mice deficient in both Egr1 and Egr3 (1/3 DKO) and a partial differention block in the immature double negative (DN) stage. In addition, thymocytes are an easily manipulatable cell type, and the DN subpopulation affected in 1/3 DKO mice can be isolated to very high purity. We anticipate that 1/3 DKO thymocytes will provide an excellent experimental system that will provide insight into Egr-dependent transcription in neuronal development, activation, and death.
Publication Title
Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival.
Sample Metadata Fields
No sample metadata fields
View Samples