Multi-faceted dissection of innate myeloid cell heterogeneity: a translational approach for application in patient care

Abstract

A broad dissection of innate myeloid cell subsets and their maturational relationships, to develop standardized tools for patient care. Several mass-spectrometry-based proteomics workflows were evaluated to iteratively select the best procedure for MS-based proteomics on small numbers of closely-related cells. The best performing method was defined based on several factors, including ease to use, costs, processing time and reproducibility, to select a method suitable for diagnostics. This method was applied on monocytic populations derived from diverse human tissues and combined with cytometry-based methods to define the immunophenotypic, proteomic and functional profiles of all monocytic subsets. The results and insights of this extensive investigation resulted in the design and validation of a flow cytometric combination of markers suitable for detection of all monocytic and dendritic cell subsets in human peripheral blood, by research and diagnostic-certified cytometers.. Overall, this thesis improved the understanding of heterogeneity and maturational relationships of innate myeloid cells and aimed for use of these cells as a screening tool in patient care and diagnostics.