Tools and Concepts for Interrogating and Defining Cellular Identity

Defining the mechanisms that generate specialized cell types and coordinate their functions is critical for understanding organ development and renewal. New tools and discoveries are challenging and refining our definitions of a cell type. A rapidly growing toolkit for single-cell analyses has expanded the number of markers that can be assigned to a cell simultaneously, revealing heterogeneity within cell types that were previously regarded as homogeneous populations. Additionally, cell types defined by specific molecular markers can exhibit distinct, context-dependent functions; for example, between tissues in homeostasis and those responding to damage. Here we review the current technologies used to identify and characterize cells, and we discuss how experimental and pathological perturbations are adding increasing complexity to our definitions of cell identity. Cellular identity can be highly plastic and influenced by different physiological contexts and tools used to measure it. Here McKinley et al. review the rapidly expanding toolkit that can be used to identify and probe cellular features and functions and discuss how those properties change in different contexts.