High-Content Immunophenotyping and Hierarchical Clustering Reveal Sources of Heterogeneity and New Surface Markers of Human Blood Monocyte Subsets
| Autor: | Christian Troidl, Annkathrin zur Heiden, Nora Staubach, Till Keller, Sandra Voss, David Kost, Oliver Dörr, Christoph Lipps, Helge Möllmann, Christian W. Hamm, Jedrzej Hoffmann, Christoph Liebetrau, Karel Fiser, Holger Nef |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD96 CD14 Lipopolysaccharide Receptors Computational biology Cell Separation 030204 cardiovascular system & hematology CD38 Biology Monocytes Flow cytometry Immunophenotyping 03 medical and health sciences 0302 clinical medicine medicine Cluster Analysis Humans Inflammation medicine.diagnostic_test Monocyte Receptors IgG Hematology Biodiversity Atherosclerosis Flow Cytometry Phenotype Hierarchical clustering High-Throughput Screening Assays 030104 developmental biology medicine.anatomical_structure Blood Circulation Biomarkers |
| Zdroj: | Thrombosis and haemostasis. 120(1) |
| ISSN: | 2567-689X |
| Popis: | Objective Blood monocyte subsets are emerging as biomarkers of cardiovascular inflammation. However, our understanding of human monocyte heterogeneity and their immunophenotypic features under healthy and inflammatory conditions is still evolving. Rationale In this study, we sought to investigate the immunophenome of circulating human monocyte subsets. Methods Multiplexed, high-throughput flow cytometry screening arrays and computational data analysis were used to analyze the expression and hierarchical relationships of 242 specific surface markers on circulating classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes in healthy adults. Results Using generalized linear models and hierarchical cluster analysis, we selected and clustered epitopes that most reliably differentiate between monocyte subsets. We validated existing transcriptional profiling data and revealed potential new surface markers that uniquely define the classical (e.g., BLTR1, CD35, CD38, CD49e, CD89, CD96), intermediate (e.g., CD39, CD275, CD305, CDw328), and nonclassical (e.g., CD29, CD132) subsets. In addition, our analysis revealed phenotypic cell clusters, identified by dendritic markers CMRF-44 and CMRF-56, independent of the traditional monocyte classification. Conclusion These results reveal an advancement of the clinically applicable multiplexed screening arrays that may facilitate monocyte subset characterization and cytometry-based biomarker selection in various inflammatory disorders. |
| Databáze: | OpenAIRE |
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