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However, the reprogramming pathway for fully reprogrammed DA neurons remains largely unclear, resulting in immature and dead\u2010end states with low efficiency. In this study, using single\u2010cell RNA sequencing, the trajectory of reprogramming DA neurons at multiple time points, identifying a continuous pathway for their reprogramming is analyzed. It is identified that intermediate cell populations are crucial for resetting host cell fate during early DA neuronal reprogramming. Further, longitudinal dissection uncovered two distinct trajectories: one leading to successful reprogramming and the other to a dead end. Notably, Arid4b, a histone modifier, as a crucial regulator at this branch point, essential for the successful trajectory and acquisition of mature dopaminergic neuronal identity is identified. Consistently, overexpressing Arid4b in the DA neuronal reprogramming process increases the yield of iDA neurons and effectively reverses the disease phenotypes observed in the PD mouse brain. Thus, gaining insights into the cellular trajectory holds significant importance for devising regenerative medicine strategies, particularly in the context of addressing neurodegenerative disorders like Parkinson's disease.<\/jats:p>","DOI":"10.1002\/advs.202403105","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T03:50:58Z","timestamp":1726458658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Epigenetic Dynamics in Reprogramming to Dopaminergic Neurons for Parkinson's Disease"],"prefix":"10.1002","volume":"11","author":[{"given":"Byounggook","family":"Cho","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cells &amp; Cell Reprogramming Department of Chemistry and Biomedical Engineering Dongguk University  Seoul 04620 Republic of 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