Epigenetic Dynamics in Reprogramming to Dopaminergic Neurons for Parkinson's Disease

Abstract: Direct lineage reprogramming into dopaminergic (DA) neurons holds great promise for the more effective production of DA neurons, offering potential therapeutic benefits for conditions such as Parkinson's disease. However, the reprogramming pathway for fully reprogrammed DA neurons remains largely unclear, resulting in immature and dead‐end states with low efficiency. In this study, using single‐cell 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.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Epigenetic Dynamics in Reprogramming to Dopaminergic Neurons for Parkinson's Disease ; day:16 ; month:09 ; year:2024 ; extent:13 ; Advanced science ; (16.09.2024) (gesamt 13)

Contributors, Places and Time

• Creator: Cho, Byounggook ; Kim, Junyeop ; Kim, Sumin ; An, Saemin ; Hwang, Yerim ; Kim, Yunkyung ; Kwon, Daeyeol ; Kim, Jongpil

Further information

• DOI: 10.1002/advs.202403105
• URN: urn:nbn:de:101:1-2409161408544.338121607824
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:25 AM CEST