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.
Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment.
No sample metadata fields
View SamplesWe investigated the gene expression profile of monocyte-derived macrophages and microglia following spinal cord injury. Moreover, we investigated the gene expression profole of M-CSF induced macrophages and new-born derived microglia following TGFb1 treatment. Overall design: monocyte-derived macrophages and microglia following spinal cord injury M-CSF induced macrophages and new-born derived microglia following TGFb1 treatment
Chronic exposure to TGFβ1 regulates myeloid cell inflammatory response in an IRF7-dependent manner.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing.
Specimen part
View SamplesBone marrow derived dendritic cells were generated from Ubc9[fl;-] and Ubc9[+/+] mice. After in vitro derivation in the presence of GM-CSF, dendritic cells were treated with tamoxifen for four days to cause CreERT2 activation, and induce Ubc9 floxed allele deletion. This allowed comparative transcriptomic analysis of Ubc9[+/+] and Ubc9[-/-] dendritic cells unstimulated or stimulated with 10ng/ml LPS for one hour and six hours.
Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing.
Specimen part
View SamplesThe immune system generates pathogen-tailored responses. The precise innate immune cell types and pathways that direct robust adaptive immune responses have not been fully characterized. By using fluorescent pathogens combined with massively parallel single cell RNA-seq, we comprehensively characterized the initial 48 hours of the innate immune response to diverse pathogens. We found that across all pathogens tested, most of the lymph node cell types and states showed little pathogen-specificity. In contrast, the rare antigen-positive cells displayed pathogen-specific transcriptional programs as early as 24 hours after immunization. In addition, mycobacteria activated a specific NK driven IFN? response. Depletion of NK cells and IFN? showed that IFN? initiated a monocyte specific signaling cascade, leading to production of major chemokines and cytokines that promote Th1 development. Our systems immunology approach sheds light on early events in innate immune responses and may help further development of safe and efficient vaccines. Overall design: Transcriptional profiling of single cells from pathogen-injected mouse auricular lymph nodes, generated from deep sequencing of thousands of cells, sequenced in several batches on illumina Nextseq500. For all experiments, innate immune lymph node cells were sorted accordng to the markers indicated in Samples' Characteristics "selection marker" field into 384-well MARS-seq2.0 cell capture plates. Sorting of antigen-carrying cells (Ag+) was based on the AF488-fluorescence of the pathogens injected. Different pathogens and time points were used, as indicated in the Samples' Characteristics "infection" and "time points" fields.
Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity.
Specimen part, Cell line, Subject, Time
View SamplesLangerhans cells (LCs) populate the mucosal epithelium, a major entry portal for pathogens, yet their ontogeny remains unclear. In contrast to skin LCs originating from self-renewing radioresistant embryonic precursors, we found that oral mucosal LCs derive from circulating radiosensitive precursors. Mucosal LCs can be segregated into CD103+CD11blow (CD103+LCs) and CD11b+CD103- (CD11b+LCs) subsets. We further demonstrated that similar to non-lymphoid dendritic cells (DCs), CD103+LCs originate from pre-DCs, whereas CD11b+LCs differentiate from both pre-DCs and monocytic precursors. Despite this ontogenetic discrepancy between skin and mucosal LCs, transcriptomic signature and immunological function of oral LCs highly resemble those of skin LCs but not DCs. These findings, along with their epithelial position, morphology and expression of LC-associated phenotype strongly suggest that oral mucosal LCs are genuine LCs. Collectively, in a tissue-dependent manner, murine LCs differentiate from at least three distinct precursors (embryonic, pre-DCs and monocytic) in steady state Overall design: The following cells were isolated from mice (2-4 replicates): Lung DCs, mucosal CD103+ LC, mucosal CD11b+ LC, Skin LC. Transcriptome analysis was performed.
Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes.
No sample metadata fields
View SamplesWe report on the regulation of transcripts following siRNA-mediated depletion of an RNA binding protein, CELF1, in primary chicken embryonic cardiomyocytes in culture. Overall design: Cultured chicken primary embryonic cardiomyocytes (isolated from embryonic day 8 hearts) were transfected with siRNA against CELF1 (n=3) or mock transfected (n=3) at 24 hours in culture.
Identification of Targets of CUG-BP, Elav-Like Family Member 1 (CELF1) Regulation in Embryonic Heart Muscle.
Specimen part, Treatment, Subject
View SamplesBackground: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder.
Identification of the BRD1 interaction network and its impact on mental disorder risk.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Corrigendum: Deterministic direct reprogramming of somatic cells to pluripotency.
Specimen part
View SamplesSomatic cells can be directly reprogrammed to pluripotency by exogenous expression of transcription factors, classically Oct4, Sox2, Klf4 and c-Myc. While distinct types of somatic cells can be reprogramed with varying efficiencies and by different modified reprogramming protocols, induced pluripotent stem cell (iPSC) induction remains inefficient and stochastic where a fraction of the cells converts into iPSCs. The nature of rate limiting barrier(s) preventing majority of cells to convert into iPSCs remains elusive. Here we show that neutralizing Mbd3, a core member of the Mbd3/NURD co-repressor and chromatin-remodeling complex, results in deterministic and synchronized reprogramming of multiple differentiated cell types to pluripotency. 100% of Mbd3 depleted mouse and human somatic cells convert into iPSCs after seven days of reprogramming factor induction. Our findings delineate a critical pathway blocking the reestablishment of pluripotency, and offer a novel platform for future dissection of epigenetic dynamics leading to iPSC formation at high resolution.
Deterministic direct reprogramming of somatic cells to pluripotency.
Specimen part
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