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In contrast, the neonatal mouse heart possesses a regenerative capacity governed by CM proliferation; however, a metabolic switch from glycolysis to fatty acid oxidation during post-natal development results in loss of this regenerative capacity. Interestingly, a sarcomere isoform switch also takes place during post-natal development where slow skeletal troponin I (ssTnI) is replaced with cardiac troponin I (cTnI). It remains unclear whether there is an interplay between sarcomere isoform switching, cardiac metabolism, and regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this study, we employ proteomics, metabolomics, and lipidomics, transgenic mice, MI models, and histological analysis to delineate the molecular and sarcomeric transitions that occur during cardiac maturation and regeneration. First, we utilize integrated quantitative bottom\u2013up and top\u2013down proteomics to comprehensively define the proteomic and sarcomeric landscape during post-natal heart maturation. By employing a CM-specific ssTnI transgenic mouse model, we discovered that ssTnI overexpression increased CM proliferation and the cardiac regenerative capacity of the post-natal heart following MI compared to control mice by histological analysis. Our global proteomic analysis of ssTnI transgenic mice following MI reveals that ssTnI overexpression induces a significant shift in the cardiac proteomic landscape. Additionally, our lipidomic analysis demonstrated a significant up-regulation of lipid species in the transgenic mice. This proteomic shift is characterized by an up-regulation of key proteins involved in glycolytic metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, our data suggest that the post-natal TnI isoform switch may play a role in the metabolic shift from glycolysis to fatty acid oxidation during post-natal maturation. This underscores the significance of a sarcomere-metabolism axis during CM proliferation and heart regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf069","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T05:25:45Z","timestamp":1744867545000},"page":"1240-1253","source":"Crossref","is-referenced-by-count":6,"title":["Integrated proteomics identifies troponin I isoform switch as a regulator of a sarcomere-metabolism axis during cardiac regeneration"],"prefix":"10.1093","volume":"121","author":[{"given":"Timothy J","family":"Aballo","sequence":"first","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]},{"name":"Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyoung","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Oklahoma State University , Stillwater, OK 74078 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt G","family":"Paltzer","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Perciaccante","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa R","family":"Pergande","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J","family":"Salamon","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakota J","family":"Nuttall","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan W","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]},{"name":"Department of Chemistry, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]},{"name":"Human Proteomics Program, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1528-7393","authenticated-orcid":false,"given":"Ahmed I","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, 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