Phenotypic plasticity in fish cell lines: conceptual links to aquatic epigenetics

Fish cell lines have long supported aquatic research, yet their emerging role as seed cells for cultured seafood requires a deeper understanding of their phenotypic stability. Although these cells often demonstrate prolonged proliferation and relative resistance to culture-associated senescence, they can also exhibit marked culture-dependent variability. In this review, I examine a central feature of fish cell culture: the coexistence of durable growth and flexible cell states. By focusing on spontaneous immortalization, passage-dependent changes, and differentiation-related plasticity, particularly in muscle and adipose lineages, I consider how these phenomena may be interpreted through the lens of epigenetic plasticity. Direct epigenomic evidence remains limited, and this review therefore presents a hypothesis-generating conceptual framework rather than an established mechanistic model. Nevertheless, studies involving DNA demethylation, incomplete senescence programs, possible differences in senescence-related genomic context, environmental epigenetics, and nuclear organization provide conceptual clues that reversible regulatory processes above the level of DNA sequence may shape fish cell-state behavior. I further discuss how this perspective is relevant to aquatic biotechnology and cultured seafood, where reproducibility, lineage control, quality control, and process standardization depend on monitoring cell-state behavior while distinguishing reversible regulatory changes from genetic alterations acquired during long-term culture. Clarifying the regulatory processes associated with phenotypic plasticity in fish cell lines may therefore provide a useful foundation for future epigenomic studies and for the development of biologically reliable fish cell platforms.