{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:56:02Z","timestamp":1785426962965,"version":"3.56.0"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Quzhou technology projects","award":["2025K063"],"award-info":[{"award-number":["2025K063"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32403021"],"award-info":[{"award-number":["32403021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32403021"],"award-info":[{"award-number":["32403021"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Zebrafish fin regeneration serves as a classic model for investigating vertebrate tissue regeneration, yet the core regulatory networks and their crosstalk with the immune microenvironment remain incompletely characterized. This study aimed to identify hub genes, and elucidate the underlying molecular mechanisms and immune microenvironment dynamics during zebrafish fin regeneration. Methods: We integrated multiple bulk RNA-seq datasets of zebrafish fin regeneration from the GEO database, followed by data standardization with batch effect removal. Hub genes were screened via differential expression analysis, weighted gene co-expression network analysis (WGCNA), and predictive models constructed with 13 classic machine learning algorithms. Functional enrichment, time-ordered gene co-expression network (TO-GCN) method, immune infiltration analyses and RT-qPCR validation were further performed. Results: We identified upregulated differentially expressed genes, regeneration-correlated gene modules and their overlapping genes, including 82 candidate genes and 10 hub genes enriched in cytoskeleton remodeling, extracellular matrix organization, and focal adhesion. Temporal analysis uncovered hierarchical gene regulation and functional switching during regeneration. Hub gene expression was significantly correlated with the infiltration of B cells, M1\/M2 macrophages and CD8+ T cells, revealing a stage-specific immune microenvironment. RT-qPCR validation showed high consistency with the multi-omics data. Conclusions: This study provides potential gene targets for understanding zebrafish fin regeneration, and offers a valuable reference for investigating the crosstalk between regulatory networks and the immune microenvironment in vertebrate tissue regeneration.<\/jats:p>","DOI":"10.3390\/genes17050503","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:40:12Z","timestamp":1777981212000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine Learning-Based Identification of Hub Genes and Temporal Regulation Mechanisms in Zebrafish Fin Regeneration"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiaoying","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junli","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Shu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital, Quzhou 324000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nature08899","article-title":"Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation","volume":"464","author":"Jopling","year":"2010","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"eaaz3090","DOI":"10.1126\/science.aaz3090","article-title":"Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates","volume":"369","author":"Wang","year":"2020","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tsata, V., and Wehner, D. 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