An overview of cell phenotypes in HCS: limitations and advantages

High-content screening (HCS) defines a series of cell-based multiparametric approaches for analysis at the single-cell level. In recent years, HCS has been increasingly pursued in the drug discovery field, adding to the repertoire of assay type, or increasing throughput in applications such as compound screening and mechanism of action studies, as well as for target identification/validation (siRNA screening). Obviously, as cells represent the objects of high-content assays, the outcome of any HCS assay is determined by the cell type: the choice of the most suitable cellular model for a given assay is a critical step that must follow biological and technical criteria.

Here, I discuss these criteria and report a systematic survey of cell types used so far in HCS, with particular emphasis on their strengths and drawbacks. I also illustrate my expectations for future advances on cellular models used in HCS.

Despite the plethora of cell types potentially suitable for HCS, so far only a handful of cellular models (particularly human cancer cell lines) account for the great majority of HCS assays. In the future, the introduction of novel cell types, including engineered and primary cells, will further expand the potential of HCS for systems biology and drug discovery.