Toward a General Quantity of Cellular State: Cell Culture Scaffolds as Case Studies

抄録

Cultured cells are usually described by thousands of molecular measurements, yet few quantities provide a general and interpretable summary of cellular state across experiments. Here, we evaluated Liberality, calculated as the Shannon entropy of relative raw RNA-seq counts, using public transcriptomic datasets involving extracellular matrices, three-dimensional scaffolds, substrate stiffness, endothelial differentiation, and serial passage. Across heterogeneous systems, Liberality showed reproducible condition-associated differences linked to hepatocyte maturation, matrix-dependent responses, hepatic stellate-cell activation, lineage commitment, and adaptation to prolonged culture. Differentiation and maturation were generally associated with lower Liberality, whereas culture adaptation and dedifferentiation were associated with higher values. Scaffold effects depended on cellular background and were often smaller than changes accompanying major shifts in cell identity. These findings suggest that Liberality may capture a broad property of transcriptomic organization rather than the activity of any single pathway. Historically, tissue culture developed both to isolate cells from systemic variation and, more recently, to reconstruct in vivo-like environments through scaffolds and microphysiological systems. Liberality may help quantify movement between these poles. It should be regarded as a candidate descriptor rather than a universal measure and requires prospective validation against related entropy metrics and technical confounders.