What is the Cell Types Tool?

One of challenges when developing experiments for single cell analysis platforms like CyTOF, single cell sequencing and flow cytometry is how to choose which marker combinations are essential in defining cell subsets. If too few markers are used in an assay, the risk is that downstream populations and their function will be unwittingly contaminated with other cell subsets.

A common example is the classical, non-classical and intermediate monocyte populations that are defined by CD14 vs CD16. If NK cells are not previously gated out of the analysis, the CD16+/CD14 lo non-classical monocyte population is often contaminated with NK cells. Similarly, there are many markers we rely upon in immunophenotyping cell subsets that are more widely expressed on multiple cell subsets than we might consider. For example, CD11c is a common marker used to delineate conventional dendritic cell subsets. However, activated B cells also express CD11c. If CD11c is excluded early in analysis, this population will be lost from downstream analysis.

There are few online resources that provide a condensed view of essential markers and recommended gate logic and that are kept up to date with our ever-growing understanding of the immune system. FluoroFinder is compiling multiple cell subset hierarchies to guide marker choice in these assays in an online resource called the Cell Types Tool. Currently, we offer a graphical interface for B cell maturation, Hematopoiesis, T cell subsets, T cell maturation and General Immune subsets.

FluoroFinder is also an integral partner to the SOULCAP Foundation, an effort to standardize essential marker combinations, ontology, naming and analysis in flow cytometry. These online tools are regularly updated to conform with SOULCAP recommendations which at this time covers all immunological subsets found in human peripheral blood. Eventually this tool will continue to grow in marker relevance in other experimental models, like mouse, and in other tissue types, like secondary lymphoid tissues and bone marrow.

There are some research areas, like hematopoiesis, B and T cell maturation, where the
consensus for marker combinations is less definitive, especially in human where healthy
bone marrow and spleen are more difficult samples to obtain. For example, the
relationship between different lymphocyte progenitors is not clearly defined. In the
literature, three progenitors, lymphoid-primed multipotent progenitor, common lymphoid
progenitor and multi-lymphoid progenitors were not originally defined using the same
marker combinations and much empirical definition is still required. Thus, the Cell Types ToolTool, in these instances, is a helpful guide that in addition to the graphical interface to
visualize the interconnected nature of their etiology, offers extensive bibliographies of
the references utilized to build the hierarchical map. A review of the publications is also
offered as a written assay at the top of the page of each tool.