{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:42:59Z","timestamp":1791556979553,"version":"4.3.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Epigenet. Epigenom."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/freae.2026.1867376","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:10:15Z","timestamp":1782252615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Phenotypic plasticity in fish cell lines: conceptual links to aquatic epigenetics"],"prefix":"10.3389","volume":"4","author":[{"given":"Daisuke","family":"Ikeda","sequence":"first","affiliation":[{"name":"School of Marine Biosciences, Kitasato University","place":["Sagamihara, Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.4161\/epi.24178","article-title":"Temperature affects methylation of the myogenin putative promoter, its expression and muscle cellularity in Senegalese sole larvae","volume":"8","author":"Campos","year":"2013","journal-title":"Epigenetics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1186\/1471-2164-15-525","article-title":"Thermal plasticity of the miRNA transcriptome during Senegalese sole development","volume":"15","author":"Campos","year":"2014","journal-title":"BMC Genomics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/cddiscovery.2017.3","article-title":"Characterization and isolation of highly purified porcine satellite cells","volume":"3","author":"Ding","year":"2017","journal-title":"Cell Death Discov."},{"key":"B4","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3389\/fgene.2013.00159","article-title":"Sarcopenia and piscines: the case for indeterminate-growing fish as unique genetic model organisms in aging and longevity research","volume":"4","author":"Froehlich","year":"","journal-title":"Front. 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