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

As a critical interface for metal hyperaccumulation,
the multicellular
complexity of oyster gills poses a challenge in studying their metal
uptake and detoxification mechanisms. Here, we constructed the first
cell atlas of oyster gills at single-cell resolution level, identifying
a total of 18 cell types. Single-cell transcriptomic analysis of gills
from oysters with high and low Cu accumulation revealed the cellular
regulatory network underlying intraspecific differences in metal accumulation.
For the first time, Cu-specific accumulating copperphilic cells in
the oyster gills were identified, and a direct correlation was confirmed
between copperphilic cell abundance and Cu content (R2 =
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.