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SRP049942
Mus musculus
26 Downloadable Samples
Illumina HiSeq 1500
Description
Macrophages are hematopoietic cells critical for innate immune defense, but also control organ homeostasis in a tissue-specific manner. Tissue-resident macrophages, therefore, provide a well-defined model to study the impact of ontogeny and microenvironment on chromatin state. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations, as well as monocytes and neutrophils. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes. Our work suggests that a combination of tissue and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment has the capacity to alter the chromatin landscape of macrophages derived from transplanted adult bone marrow in vivo and even differentiated macrophages are reprogramed when transferred into a new tissue. Altogether, these data provide a comprehensive view of macrophage regulation and highlight the importance of microenvironment along with pioneer factors in orchestrating macrophage identity and plasticity. Overall design: 7 tissue-resident macrophage populations were isolated, as well as monocytes and neutrophils, and transcriptome analysis was performed. Experiment was done in duplicates.
Publication Title
Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identity and functions remain poorly defined. In this study we characterized the phenotype, life-cycle and function of different conventional dendritic cells (cDC) populations in the heart, with focus on the 2 major subsets (CD103+ and CD11b+), which differentially rely on local proliferation and precursor recruitment to maintain tissue residency. Following viral infection of the myocardium, cDCs accumulate in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages. cDC depletion abrogates antigen-specific CD8+ T cell proliferative expansion, transforming subclinical cardiac injury to overt heart failure. Importantly, these effects are mediated by BATF3-dependent CD103+ cDCs. Collectively, our findings definitively identify resident cardiac cDC subsets, define their origins, and implicate an essential role for CD103+ cDCs in antigen-specific T cell responses during viral myocarditis.
Publication Title
A CD103<sup>+</sup> Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Control (CRL2429 C11) and A-T (MC3/AT30) iPSC were differentiated according to Erceg et al to generate cerebellar precursors Overall design: Examination of changes in gene expression after a 34 day differentiation protocol in control and A-T iPSC
Publication Title
Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSC) sustain long-term reconstitution of hematopoiesis in primary transplantation recipients. Few HSC can serially reconstitute secondary recipients, and their identity and contribution to normal hematopoiesis remain moot. We directed transgene expression to a distinct fraction of HSC in the adult bone marrow. Epxression of the reporter transgene segregated with reconstituting activity during secondary transplantations. The labeled cells had an undifferentiated phenotype and expression profile, were slow-cycling and localized to the vascular niche. Inducible genetic labeling showed the transgene-expressing HSC gave rise to other cells within the HSC populations, confirming their top position in the differentiation hierarchy. Importantly, labeled HSC gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be further accelerated by interferon response. Thus, the rare "top-level" HSC with serial reconstitution capacity also serve as the major source of endogenous hematopoiesis in adult animals. Overall design: Sorted LSK CD48- CD150+ Map17-GFP+ and Map17-GFP- HSCs and LSK CD48+ CD150- Map17-GFP-MPPs were sequenced for mRNA profiling.
Publication Title
Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
To identify genes affected by mutant huntington protein, we performed mRNA-seq experiments with Striatal STHdh Q7/Q7, Q7Q111, and Q111/Q111 cells. We also tested the effect of Sp1 overexpression on rescuing gene expression in Q111/Q111 cells. Overall design: Striatal STHdh Q7/Q7, Q7/Q111 and Q111/Q111 cells were used for the mRNA-seq in replicates. After Sp1 transient overexpression in Q111/Q111 cells, cells were collected for mRNA-seq analysis.
Publication Title
Real-time imaging of Huntingtin aggregates diverting target search and gene transcription.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
S-adenosylmethionine levels regulate the schwann cell DNA methylome.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
DNA methylation is a key epigenetic regulator of mammalian embryogenesis and somatic cell differentiation. Using high-resolution genome-scale maps of methylation patterns, we show that the formation of myelin in the peripheral nervous system, proceeds with progressive DNA demethylation, which coincides with an upregulation of critical genes of the myelination process. More importantly, we found that, in addition to expression of DNA methyltransferases and demethylases, the levels of S-adenosylmethionine (SAMe), the principal biological methyl donor, could also play a critical role in regulating DNA methylation during myelination and in the pathogenesis of diabetic neuropathy. In summary, this study provides compelling evidence that SAMe levels need to be tightly controlled to prevent aberrant DNA methylation patterns, and together with recently published studies on the influence of SAMe on histone methylation in cancer and embryonic stem cell differentiation show that in diverse biological processes, the methylome, and consequently gene expression patterns, are critically dependent on levels of SAMe.
Publication Title
S-adenosylmethionine levels regulate the schwann cell DNA methylome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mutation of senataxin alters disease-specific transcriptional networks in patients with ataxia with oculomotor apraxia type 2.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional role of senataxin in disease, we examined differential gene expression in AOA2 patient fibroblasts, identifying a core set of genes showing altered expression by microarray and RNA-sequencing. To determine whether AOA2 and ALS4 mutations differentially affect gene expression, we overexpressed disease-specific SETX mutations in senataxin-haploinsufficient fibroblasts and observed changes in distinct sets of genes. This implicates mutation-specific alterations of senataxin function in disease pathogenesis and provides a novel example of allelic neurogenetic disorders with differing gene expression profiles. Weighted gene co-expression network analysis (WGCNA) demonstrated these senataxin-associated genes to be involved in both mutation-specific and shared functional gene networks. To assess this in vivo, we performed gene expression analysis on peripheral blood from members of 12 different AOA2 families and identified an AOA2-specific transcriptional signature. WGCNA identified two gene modules highly enriched for this transcriptional signature in the peripheral blood of all AOA2 patients studied. These modules were disease-specific and preserved in patient fibroblasts and in the cerebellum of Setx knockout mice demonstrating conservation across species and cell types, including neurons. These results identify novel genes and cellular pathways related to senataxin function in normal and disease states, and implicate alterations in gene expression as underlying the phenotypic differences between AOA2 and ALS4.
Publication Title
Mutation of senataxin alters disease-specific transcriptional networks in patients with ataxia with oculomotor apraxia type 2.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta
- 78 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The hippocampus is part of a brain network essential for memory function. Paradoxically, the hippocampus is also the brain structure that is most sensitive to hypoxic-ischemic episodes. Here we show that the expression of genes associated with glycolysis and glutamate metabolism in astrocytes and the coverage of excitatory synapses by astrocytic processes undergo significant decreases in the CA1 field of the monkey hippocampus during postnatal development. Given the established role of astrocytes in the regulation of glutamate concentration in the synaptic cleft, our findings indicate that a developmental decrease in astrocytic processes underlies the selective vulnerability of CA1 during hypoxic-ischemic episodes in adulthood, its decreased susceptibility to febrile seizures with age, as well as contribute to the emergence of selective, adult-like memory function.
Publication Title
Developmental regulation of gene expression and astrocytic processes may explain selective hippocampal vulnerability.
Sample Metadata Fields
Specimen part
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