Similar Datasets
Project description:The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here, we profiled >25,000 differentiating and mature mouse neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function and fate decision in their steady state and during bacterial infection. Eight neutrophil populations were defined by distinct molecular signatures. The three mature peripheral blood neutrophil subsets arise from distinct maturing bone marrow neutrophil subsets. Driven by both known and uncharacterized transcription factors, neutrophils gradually acquire microbicidal capability as they traverse the transcriptional landscape, representing an evolved mechanism for fine-tuned regulation of an effective but balanced neutrophil response. Bacterial infection reprograms the genetic architecture of neutrophil populations, alters dynamic transitions between subpopulations and primes neutrophils for augmented functionality without affecting overall heterogeneity. In summary, these data establish a reference model and general framework for studying neutrophil-related disease mechanisms, biomarkers and therapeutic targets at single-cell resolution.
| S-EPMC7442692 | biostudies-literature
Project description:The full neutrophil heterogeneity and differentiation landscape remains incompletely characterized. Here we profiled more than 25,000 mouse differentiating and mature neutrophils using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function, and fate decision in their steady state and during bacterial infection. Eight neutrophil populations (including the GMP population) were defined by distinct molecular signatures, including a new circulating mature neutrophil population highly expressing interferon-stimulated genes. The three mature peripheral blood neutrophil subsets arise from distinct maturing bone marrow neutrophil subsets, a novel mechanism that highlights the complex and precise regulation of neutrophil production. Neutrophil heterogeneity and differentiation are driven by both known and uncharacterized transcription factors. Neutrophils gradually acquire microbicidal capability as cells traverse the transcriptional landscape, representing an evolved mechanism for fine-tuned regulation of an effective but balanced neutrophil response. Bacterial infection reprograms the genetic architecture of neutrophil population, alters dynamic transition between each subpopulation, and primes neutrophils for augmented functionality without affecting overall heterogeneity. Bacterial infection-induced emergency granulopoiesis is mediated by augmented proliferation of early-stage neutrophil progenitors and accelerated post-mitotic maturation. In summary, single-cell transcriptomics enabled the reconstruction of neutrophil differentiation and maturation trajectories and uncovered neutrophil subpopulations, gene pathways, and regulators of neutrophil function and fate decisions. These data establish a reference model and general framework for studying neutrophil-related disease mechanisms, biomarkers, and therapeutic targets at single-cell resolution.
2020-05-27 | GSE137539 | GEO
Project description:Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection
| PRJNA565802 | ENA
Project description:Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection
| PRJNA565803 | ENA
Project description:The pathophysiological mechanisms, especially the roles of immune cells, underlying early stages of severe burn injury have not yet been fully clarified. Here, we analyzed circulating neutrophils (PMNs) in healthy donors and early burned patients by single-cell RNA sequencing to provide a comprehensive transcriptional landscape of PMNs in heterogeneity and functional multiplicity. Circulating PMNs in the healthy donors and burned groups were divided into five subgroups (G3, G4, G5a, G5b, G5c) with different functions. The dominant subsets of PMNs in homeostasis and burn injury significantly differed between groups. In addition, cells in the same subpopulation had the same core identity markers but performed different functions in healthy and burned states. Under burned conditions, PMN activation was very evident and accompanied by clear degranulation and metabolic abnormalities. Interestingly, was found that PMN activation, degranulation, chemotaxis, phagocytosis and reactive oxygen species (ROS) production in burned patients significantly differed between day 1 and days 2 or 3, thus providing a theoretical basis for PMN interventions in early burn stages. Significantly, previously undescribed transcription factors were also identified, including ZNF-787, ZNF-467, ZNF-189, ZNF-770, ZNF-262. In conclusion, this study conducted for the first time a detailed analysis of the heterogeneity and functional multiplicity of PMNs in early stages of severe burn injuries. Our findings attempted to clarify the influence of PMN heterogeneity on the pathophysiology and related mechanisms of burn injuries, which can provide new ideas for further research in burn intervention.
| S-EPMC8803731 | biostudies-literature
Project description:Retinoblastoma is a childhood retinal tumour that is the most common primary malignant intraocular tumour. However, it has been challenging to identify the cell types associated with genetic complexity. Here, we performed single-cell RNA sequencing on 14,739 cells from two retinoblastoma samples to delineate the heterogeneity and the underlying mechanism of retinoblastoma progression. Using a multiresolution network-based analysis, we identified two major cell types in human retinoblastoma. Cell trajectory analysis yielded a total of 5 cell states organized into two main branches, and the cell cycle-associated cone precursors were the cells of origin of retinoblastoma that were required for initiating the differentiation and malignancy process of retinoblastoma. Tumour cells differentiation reprogramming trajectory analysis revealed that cell-type components of multiple tumour-related pathways and predominantly expressed UBE2C were associated with an activation state in the malignant progression of the tumour, providing a potential novel "switch gene" marker during early critical stages in human retinoblastoma development. Thus, our findings improve our current understanding of the mechanism of retinoblastoma progression and are potentially valuable in providing novel prognostic markers for retinoblastoma.
| S-EPMC8611004 | biostudies-literature
Project description:Vascular endothelial cells (ECs) are increasingly recognized as active players in intercellular crosstalk more than passive linings of a conduit for nutrition delivery. Yet, their functional roles and heterogeneity in skin remain uncharacterized. We have used single-cell RNA sequencing (scRNA-seq) as a profiling strategy to investigate the tissue-specific features and intra-tissue heterogeneity in dermal ECs at single-cell level. Methods: Skin tissues collected from 10 donors were subjected to scRNA-seq. Human dermal EC atlas of over 23,000 single-cell transcriptomes was obtained and further analyzed. Arteriovenous markers discovered in scRNA-seq were validated in human skin samples via immunofluorescence. To illustrate tissue-specific characteristics of dermal ECs, ECs from other human tissues were extracted from previously reported data and compared with our transcriptomic data. Results: In comparison with ECs from other human tissues, dermal ECs possess unique characteristics in metabolism, cytokine signaling, chemotaxis, and cell adhesions. Within dermal ECs, 5 major subtypes were identified, which varied in molecular signatures and biological activities. Metabolic transcriptome analysis revealed a preference for oxidative phosphorylation in arteriole ECs when compared to capillary and venule ECs. Capillary ECs abundantly expressed HLA-II molecules, suggesting its immune-surveillance role. Post-capillary venule ECs, with high levels of adhesion molecules, were equipped with the capacity in immune cell arrest, adhesion, and infiltration. Conclusion: Our study provides a comprehensive characterization of EC features and heterogeneity in human dermis and sets the stage for future research in identifying disease-specific alterations of dermal ECs in various dermatoses.
| S-EPMC8120211 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-13 | GSE171029 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-11-09 | GSE112091 | GEO
Project description:Neutrophil is known to critically impact the development of renal diseases (e.g., the clear cell renal cell carcinoma (ccRCC)), whereas the heterogeneity of neutrophils in ccRCC remains unclear. In the present study, kidney biopsies from healthy donors and ccRCC tissues were collected for single-cell RNA sequencing (scRNA-seq). In addition, the subpopulations of neutrophils in a healthy kidney and in the tumor microenvironment (TME) of ccRCC were expressed and then analyzed. The genes reported previously were mapped to all subpopulations identified here. On that basis, biological theme comparison and Gene Set Enrichment Analysis (GSEA) were employed to reveal and compare relevant biological functions. In a healthy kidney, neutrophils exhibit two subpopulations: one is more associated with renal autoimmunity, probably acting as therapeutic target; the other is suggested to resist infectious microorganisms. It is noteworthy that six subpopulations were identified in ccRCC biopsy, and two were more relevant to autoimmunity, while the other four are more relevant to the tumor pathology. Besides, ccRCC neutrophil could resist anticancer immune therapies of ipilimumab and pembrolizumab for their low/no expressions of CTLA-4, PD-1, and PD-L1. Thus, this study can help understand the heterogeneity and pathological significance of neutrophils in renal diseases.
| S-EPMC7984911 | biostudies-literature