Alignment of classical cell type definitions with molecular signatures

Determine the extent to which morphology- and phenotype-based cell type classifications correspond to molecular signatures measured in cells (e.g., transcriptomic, proteomic, epigenomic profiles), in order to clarify whether traditional cell type definitions align with distinct molecular states and signatures.

Background

Within the paper’s working definitions, the authors distinguish cell states, cell types, and cell fates. They note that cell types have traditionally been defined by morphology or phenotypic characteristics, while modern single-cell and multi-omic technologies increasingly use molecular signatures to characterize cellular identities.

The authors explicitly state that the concordance between classical, morphology-based cell type definitions and molecular signatures remains unresolved. This uncertainty has practical implications for Cell Atlas projects, mechanistic modeling, and the interpretation of single-cell data, and is linked to understanding sources and propagation of molecular noise.