{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:27:26Z","timestamp":1787851646570,"version":"build-2784847793"},"reference-count":24,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Guangxi","award":["2023GXNSFBA026195"],"award-info":[{"award-number":["2023GXNSFBA026195"]}]},{"name":"Natural Science Foundation of Guangxi","award":["2026GXNSFAA00640029"],"award-info":[{"award-number":["2026GXNSFAA00640029"]}]},{"name":"Natural Science Foundation of Guangxi","award":["2026GXNSFAA00641143"],"award-info":[{"award-number":["2026GXNSFAA00641143"]}]},{"name":"Guangxi First Batch of Qingmiao Talent Funding Project"},{"name":"Scientific Research Starting Fund Project for High-level Talents of Guangxi Academy of Medical Sciences","award":["YKY-GCRC-202510"],"award-info":[{"award-number":["YKY-GCRC-202510"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Forskolin (FSK) is a well-characterized small-molecule activator of adenylyl cyclase that drives direct neuronal transdifferentiation in human fibroblasts; however, the temporal sequence and coordinated relationships among proteomic and metabolic adaptations during the initiation phase of lineage conversion remain poorly understood. In this study, we applied data-independent acquisition (DIA)-based quantitative proteomics and untargeted metabolomics on BJ human dermal fibroblasts at three biological timepoints: pre-induction (day 0), commitment onset (day 2), and neuronal maturation (day 5). Under the established FSK-based induction protocol, BJ fibroblasts rapidly acquired neuronal-like features, with more than 90% of cells becoming TUJ1-positive by day 5. Proteomic profiling revealed a profound, dichotomous regulatory shift: time-dependent activation of core metabolic and energy pathways (glycolysis, the TCA cycle, and oxidative phosphorylation) coupled with persistent suppression of cell-cycle progression and DNA replication. Concordantly, global metabolomic profiling revealed a statistically unidirectional transition in metabolic states characterized by the progressive accumulation of phosphoenolpyruvate (PEP). Collectively, our findings identify coordinated remodeling of central carbon metabolism as a prominent early molecular feature associated with neuronal transdifferentiation under the FSK-based induction protocol. This study provides an integrated proteomic and metabolomic framework for understanding early molecular remodeling during chemically induced cell fate conversion and provides a basis for future functional studies of metabolic regulation during reprogramming.<\/jats:p>","DOI":"10.3390\/cimb48090871","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:47:13Z","timestamp":1787849233000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic Proteomic and Metabolomic Analysis Reveals Metabolic Reprogramming During Early Neuronal Transdifferentiation of Human Fibroblasts Driven by Forskolin"],"prefix":"10.3390","volume":"48","author":[{"given":"Xiang","family":"Yuan","sequence":"first","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyao","family":"Pan","sequence":"additional","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4307-6211","authenticated-orcid":false,"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7189-3518","authenticated-orcid":false,"given":"Dandan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-3984","authenticated-orcid":false,"given":"Ben","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.4103\/NRR.NRR-D-24-00434","article-title":"Multi-target neural circuit reconstruction and enhancement in spinal cord injury","volume":"21","author":"Cao","year":"2026","journal-title":"Neural Regen. 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