Similar Datasets
Project description:CD4+ regulatory T cells (Tregs) activate and expand in response to many different types of injuries, suggesting that they play a critical role in controlling the host response to tissue damage. Here we use multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. CD44high Tregs expand in response to injury and are more suppressive than CD44low Tregs. T cell receptor (TCR) analysis reveal that CD44high Tregs undergo TCRαβ clonal expansion and increased CDR3 diversity in response to injury. Bulk and single-cell RNA sequencing with paired TCR clonotype analysis demonstrate that important Treg-associated genes were significantly differentially expressed in both CD44high and CD44low Tregs with expanded TCR clonotypes. CyTOF analysis verified protein expression of these genes on CD44high Tregs, with increases in Helios, Galectin-3 and PYCARD expression following injury. Collectively, these data provide new insights into CD44high Tregs, an important subset in the response to injury to tissue damage.
2022-05-01 | GSE174789 | GEO
Project description:CD4+ regulatory T cells (Tregs) activate and expand in response to many different types of injuries, suggesting that they play a critical role in controlling the host response to tissue damage. Here we use multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. CD44high Tregs expand in response to injury and are more suppressive than CD44low Tregs. T cell receptor (TCR) analysis reveal that CD44high Tregs undergo TCRαβ clonal expansion and increased CDR3 diversity in response to injury. Bulk and single-cell RNA sequencing with paired TCR clonotype analysis demonstrate that important Treg-associated genes were significantly differentially expressed in both CD44high and CD44low Tregs with expanded TCR clonotypes. CyTOF analysis verified protein expression of these genes on CD44high Tregs, with increases in Helios, Galectin-3 and PYCARD expression following injury. Collectively, these data provide new insights into CD44high Tregs, an important subset in the response to injury to tissue damage.
2022-05-01 | GSE174788 | GEO
Project description:Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells
| PRJNA731522 | ENA
Project description:Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [scRNA-seq]
| PRJNA731527 | ENA
Project description:Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [Bulk RNA-seq]
| PRJNA731526 | ENA
Project description:CD4+ regulatory T cells (Tregs) activate and expand in response to different types of injuries, suggesting that they play a critical role in controlling the immune response to tissue and cell damage. This project used multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. We show that CD44high Tregs expand in response to injury and were highly suppressive when compared to CD44low Tregs. T cell receptor (TCR) repertoire analysis revealed that the CD44high Treg population undergo TCRαβ clonal expansion as well as increased TCR CDR3 diversity. Bulk RNA sequencing and single-cell RNA sequencing with paired TCR clonotype analysis identified unique differences between CD44high and CD44low Tregs and specific upregulation of genes in Tregs with expanded TCR clonotypes. Gene ontology analysis for molecular function of RNA sequencing data identified chemokine receptors and cell division as the most enriched functional terms in CD44high Tregs versus CD44low Tregs. Mass cytometry (CyTOF) analysis of Tregs from injured and uninjured mice verified protein expression of these genes on CD44high Tregs, with injury-induced increases in Helios, Galectin-3 and PYCARD expression. Taken together, these data indicate that injury triggers the expansion of a highly suppressive CD44high Treg population that is transcriptionally and phenotypically distinct from CD44low Tregs suggesting that they actively participate in controlling immune responses to injury and tissue damage.
| S-EPMC9135044 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. We investigated global gene expression in surgical samples of brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower-grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix remodeling. We found that the gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes more highly expressed in rapidly progressing tumors that stratified GBMs into two groups that differed by >4-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus identify and validate a prognostic marker of both biologic and clinical significance and provide a series of putative markers for additional evaluation.
| S-EPMC556127 | biostudies-literature
Project description:Retinoblastoma is the most frequent intraocular malignancy in children. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using gene expression profiles, we demonstrate the existence of two major retinoblastoma subtypes that can be divided into six subgroups. Subtype 1 has higher expression of cone related genes and higher percentage of RB1 germline mutation. By contrast, subtype 2 tumors harbor more genes with ganglion/neuronal features. The dedifferentiation in subtype 2 is associated with stemness features including low immune infiltration. Gene Otology analysis demonstrates that immune response regulations and visual related pathways are the key molecular difference between subtypes. Subtype 1b has the highest risk of invasiveness across all subtypes. The recognition of these molecular subtypes shed a light on the important biological and clinical perspectives for retinoblastomas.
| S-EPMC10542806 | biostudies-literature
Project description:ObjectivesPrenatal exposure to cocaine causes cytoarchitectural alterations in the developing neocortex. Previously, we reported that cocaine inhibits neural progenitor cell proliferation through oxidative endoplasmic reticulum stress and consequent down-regulation of cyclin A, whereas cyclin A expression was increased in astrocytes. In the present study, cell type-specific responses to cocaine were further explored.MethodsGene expression profiles were examined in five types of cells obtained from the human fetal cerebral cortex at 20 weeks gestation. Cells were treated with 100 µM cocaine in vitro for 24 hr, followed by gene expression analysis using a human neural/stem cell/drug abuse-focused cDNA array, with verification by quantitative real-time RT-PCR.ResultsCocaine influenced transcription of distinct categories of genes in a cell type-specific manner. Cocaine down-regulated cytoskeleton-related genes including ezrin, γ2 actin, α3d tubulin and α8 tubulin in neural and/or A2B5+ progenitor cells. In contrast, cocaine modulated immune and cell death-related genes in microglia and astrocytes. In microglia, cocaine up-regulated the immunoregulatory and pro-apoptotic genes IL-1β and BAX. In astrocytes, cocaine down-regulated the immune response gene glucocorticoid receptor and up-regulated the anti-apoptotic genes 14-3-3 ε and HVEM. Therefore, cell types comprising the developing neocortex show differential responses to cocaine.ConclusionsThese data suggest that cocaine causes cytoskeletal abnormalities leading to disturbances in neural differentiation and migration in progenitor cells, while altering immune and apoptotic responses in glia. Understanding the mechanisms of cocaine's effects on human CNS cells may help in the development of therapeutic strategies to prevent or ameliorate cocaine-induced impairments in fetal brain development.
| S-EPMC2952961 | biostudies-literature
Project description:A major cause of human deafness and vestibular dysfunction is permanent loss of the mechanosensory hair cells of the inner ear. In non-mammalian vertebrates such as zebrafish, regeneration of missing hair cells can occur throughout life. While a comparative approach has the potential to reveal the basis of such differential regenerative ability, the degree to which the inner ears of fish and mammals share common hair cells and supporting cell types remains unresolved. Here, we perform single-cell RNA sequencing of the zebrafish inner ear at embryonic through adult stages to catalog the diversity of hair cells and non-sensory supporting cells. We identify a putative progenitor population for hair cells and supporting cells, as well as distinct hair and supporting cell types in the maculae versus cristae. The hair cell and supporting cell types differ from those described for the lateral line system, a distributed mechanosensory organ in zebrafish in which most studies of hair cell regeneration have been conducted. In the maculae, we identify two subtypes of hair cells that share gene expression with mammalian striolar or extrastriolar hair cells. In situ hybridization reveals that these hair cell subtypes occupy distinct spatial domains within the three macular organs, the utricle, saccule, and lagena, consistent with the reported distinct electrophysiological properties of hair cells within these domains. These findings suggest that primitive specialization of spatially distinct striolar and extrastriolar hair cells likely arose in the last common ancestor of fish and mammals. The similarities of inner ear cell type composition between fish and mammals validate zebrafish as a relevant model for understanding inner ear-specific hair cell function and regeneration.
| S-EPMC9851615 | biostudies-literature