Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell antigen receptor (TCR)-driven signaling initially decreased the abundance of Id3, which led to the activation of a follicular regulatory T (TFR) cell–specific transcription signature. However, sustained lower abundance of Id2 and Id3 interfered with proper development of TFR cells. Depletion of Id2 and Id3 expression in Treg cells resulted in compromised maintenance and localization of the Treg cell population. Thus, Id2 and Id3 enforce TFR cell checkpoints and control the maintenance and homing of Treg cells. Overall design: Treg mRNA profiles in lymph node from 3-week-old Id2fl/flId3fl/fl;Foxp3Cre/Cre (Id2 Id3 double-knockout) and control mice are generated by deep sequencing.
Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease.
No sample metadata fields
View SamplesGene expression profiles of mouse spinal motor neurons are compared to those in cells in posterior horn region.
R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.
Cell line
View SamplesPressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes. Overall design: Integrative analysis of single-cardiomyocyte RNA-seq of pressure-overload-induced heart failure model mice and heart failure patients with dilated cardiomyopathy, single-cell morphology, cardiac function and genetic perturbation
Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure.
Subject
View SamplesAnalysis of Pseudomonas aeruginosa PAO1 treated with 200 M sphingomyelin. Results provide insight into the response to sphingomyelin in P. aeruginosa.
Molecular mechanism for sphingosine-induced Pseudomonas ceramidase expression through the transcriptional regulator SphR.
No sample metadata fields
View SamplesActivity-dependent transcriptional profiling was performed in the basolateral amygdala in order to identify unique genetic markers for functionally distinct neuronal populations
Antagonistic negative and positive neurons of the basolateral amygdala.
No sample metadata fields
View SamplesTranscription factor Foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells
Transcription factor foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition.
Sex, Age, Specimen part, Treatment
View SamplesHistone deacetylase inhibitors (HDACis) have been shown to potentiate hippocampal-dependent memory and synaptic plasticity and to ameliorate cognitive deficits and degeneration in animal models for different neuropsychiatric conditions. However, the impact of these drugs on hippocampal histone acetylation and gene expression profiles at the genomic level, and the molecular mechanisms that underlie their specificity and beneficial effects in neural tissue, remains obscure. Here, we mapped four relevant histone marks (H3K4me3, AcH3K9,14, AcH4K12 and pan-AcH2B) in hippocampal chromatin and investigated at the whole-genome level the impact of HDAC inhibition on acetylation profiles and basal and activity-driven gene expression. HDAC inhibition caused a dramatic histone hyperacetylation that was largely restricted to active loci pre-marked with H3K4me3 and AcH3K9,14. In addition, the comparison of Chromatin immunoprecipitation sequencing and gene expression profiles indicated that Trichostatin A-induced histone hyperacetylation, like histone hypoacetylation induced by histone acetyltransferase deficiency, had a modest impact on hippocampal gene expression and did not affect the transient transcriptional response to novelty exposure. However, HDAC inhibition caused the rapid induction of a homeostatic gene program related to chromatin deacetylation. These results illuminate both the relationship between hippocampal gene expression and histone acetylation and the mechanism of action of these important neuropsychiatric drugs.
Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition.
Specimen part
View SamplesGene expression changes between outside and inside of biofilms were investigated. The gene expression was compared between the outside and inside of the biofilms. At the same time, the gene expressions were also compared with exponential phase and stationary phase in planktonic cells. The gene expression analysis showed that the physiological activities were higher at the outside of the biofilms than those at the inside of the biofilms. The genes induced at the ouside of the biofilms included genes involved in the stress responses and adhesions.
Localized expression profiles of rpoS in Escherichia coli biofilms.
No sample metadata fields
View SamplesAnterior interpositus nucleus (AIN) is a proposed site of memory formation of eyeblink conditioning. A large part of the underlying molecular events, however, remains unknown. To elucidate molecular mechanisms, we examined transcriptional changes in the AIN of mice trained with delayed-type eyeblink conditioning
Molecular evidence for two-stage learning and partial laterality in eyeblink conditioning of mice.
Sex, Specimen part
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