Novel Copper-Responsive Cell Subtypes in Oyster Gills: scRNA-Seq Uncovers Detoxification Strategy and Intraspecific Accumulation Variation

= 0.92). Trajectory analysis of cell differentiation revealed stage-specific gene module switching in metal-related cells, in which oxidative stress responses were activated in the early phase, while ion transport regulation dominated in the mature phase. Differentiation of Cu accumulation efficiency was mainly influenced by neuroendocrine-immune cells in gills maintaining physiological homeostasis, copperphilic cells selectively silencing intercellular communication, as well as ionocyte-mediated ncWNT pathway reprogramming. These results indicate a synergistic strategy by which oyster gills with high Cu accumulation enhance stress pathways (e.g., LT/RANKL) to mitigate Cu toxicity. This study provides a single-cell framework for studying the environmental adaptation and bioaccumulation mechanisms of pollutants.