What evidence would establish that a marker identifies a particular cell state?

Why

Define the state operationally, such as cycling, senescent, differentiated or activated, and choose multiple independent indicators. For a proposed senescence state, pair cell-cycle exit with morphology and additional molecular and functional readouts rather than relying on one staining assay. Test relevant known positive and negative controls, specify staining or sequencing thresholds, and look for agreement across independent biological samples.

A marker may be induced by stress, density, cell cycle or culture conditions unrelated to the claimed state. If possible, show a temporal transition and functional phenotype consistent with the label, such as diminished proliferation or a lineage-restricted response. Be cautious with population averages: two overlapping subpopulations can create the appearance of a single dual-positive state.

Validate that reagents are specific and that compensation or normalization is appropriate. Strong evidence supports an operational classification, not a universal one-to-one identity between a marker and cell state.