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Several circRNAs associated with myogenesis have been reported. However, the dynamic expression, function, and mechanism of circRNAs during myogenesis and skeletal muscle development are largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Strand\u2010specific RNA\u2010sequencing (RNA\u2010seq) and microarray datasets were used to profile the dynamic circRNAome landscape during skeletal muscle development and myogenic differentiation. Bioinformatics analyses were used to characterize the circRNAome and identify candidate circRNAs associated with myogenesis. Bulk and single\u2010cell RNA\u2010seq were performed to identify the downstream genes and pathways of circFgfr2. The primary myoblast cells, C2C12 cells, and animal model were used to assess the function and mechanism of circFgfr2 in myogenesis and muscle regeneration\n                      <jats:italic>in vitro<\/jats:italic>\n                      or\n                      <jats:italic>in vivo<\/jats:italic>\n                      by RT\u2010qPCR, western blotting, dual\u2010luciferase activity assay, RNA immunoprecipitation, RNA fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization, and chromatin immunoprecipitation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We profiled the dynamic circRNAome in pig skeletal muscle across 27 developmental stages and detected 52\u00a0918 high\u2010confidence circRNAs. A total of 2916 of these circRNAs are conserved across human, mouse, and pig, including four circRNAs (circFgfr2, circQrich1, circMettl9, and circCamta1) that were differentially expressed (|log\n                      <jats:sub>2<\/jats:sub>\n                      fold change|\u00a0&gt;\u00a01 and adjusted\n                      <jats:italic>P<\/jats:italic>\n                      value\u00a0&lt;\u00a00.05) in various myogenesis systems. We further focused on a conserved circRNA produced from the fibroblast growth factor receptor 2 (Fgfr2) gene, termed circFgfr2, which was found to inhibit myoblast proliferation and promote differentiation and skeletal muscle regeneration. Mechanistically, circFgfr2 acted as a sponge for miR\u2010133 to regulate the mitogen\u2010activated protein kinase kinase kinase 20 (Map3k20) gene and JNK\/MAPK pathway. Importantly, transcription factor Kruppel like factor 4 (Klf4), the downstream target of the JNK\/MAPK pathway, directly bound to the promoter of circFgfr2 and affected its expression via an miR\u2010133\/Map3k20\/JNK\/Klf4 auto\u2010regulatory feedback loop. RNA binding protein G3BP stress granule assembly factor 1 (G3bp1) inhibited the biogenesis of circFgfr2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present study provides a comprehensive circRNA resource for skeletal muscle study. The functional and mechanistic analysis of circFgfr2 uncovered a circRNA\u2010mediated auto\u2010regulatory feedback loop regulating myogenesis and muscle regeneration, which provides new insight to further understand the regulatory mechanism of circRNAs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12859","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:17:54Z","timestamp":1637626674000},"page":"696-712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["circRNAome profiling reveals circFgfr2 regulates myogenesis and muscle regeneration via a feedback loop"],"prefix":"10.1002","volume":"13","author":[{"given":"Junyu","family":"Yan","sequence":"first","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences  Shenzhen China"},{"name":"Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences  Shenzhen China"},{"name":"Research Centre of Animal Nutritional Genomics, State Key Laboratory of Animal Nutrition, Institute of Animal Sciences Chinese Academy of Agricultural Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Yang","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences  Shenzhen China"},{"name":"Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences  Shenzhen China"},{"name":"Research Centre of Animal Nutritional Genomics, State Key Laboratory of Animal Nutrition, Institute of Animal Sciences Chinese Academy of Agricultural Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhao","family":"Fan","sequence":"additional","affiliation":[{"name":"Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences  Shenzhen China"},{"name":"Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences  Shenzhen China"},{"name":"Research Centre of Animal Nutritional Genomics, State Key Laboratory of Animal Nutrition, Institute of Animal Sciences Chinese Academy of Agricultural Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoming","family":"Liang","sequence":"additional","affiliation":[{"name":"Research Centre of Animal Nutritional Genomics, State Key Laboratory of Animal Nutrition, Institute of Animal 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Bama China"},{"name":"Kunpeng Institute of Modern Agriculture at Foshan  Foshan 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