vitamin C-induced epigenetic modifications in donor NSCs establish midbrain marker expressions critical for cell-based therapy in Parkinson's disease
- Title
- vitamin C-induced epigenetic modifications in donor NSCs establish midbrain marker expressions critical for cell-based therapy in Parkinson's disease
- Author
- 이상훈
- Keywords
- EXPANDED MESENCEPHALIC PRECURSORS; NEURAL STEM-CELLS; L-ASCORBIC-ACID; DOPAMINE NEURONS; LONG-TERM; RAT MODEL; IN-VIVO; DIFFERENTIATION; NURR1; BRAIN
- Issue Date
- 2017-10
- Publisher
- CELL PRESS
- Citation
- STEM CELL REPORTS, v. 9, no. 4, page. 1192-1206
- Abstract
- Cultured neural stem/precursor cells (NSCs) are regarded as a potential systematic cell source to treat Parkinson's disease (PD). However, the therapeutic potential of these cultured NSCs is lost during culturing. Here, we show that treatment of vitamin C (VC) enhances generation of authentic midbrain-type dopamine (mDA) neurons with improved survival and functions from ventral midbrain (VM)-derived NSCs. VC acted by upregulating a series of mDA neuron-specific developmental and phenotype genes via removal of DNA methylation and repressive histone code (H3K9m3, H3K27m3) at associated gene promoter regions. Notably, the epigenetic changes induced by transient VC treatment were sustained long after VC withdrawal. Accordingly, transplantation of VC-treated NSCs resulted in improved behavioral restoration, along with enriched DA neuron engraftment, which faithfully expressed midbrain-specific markers in PD model rats. These results indicate that VC treatment to donor NSCs could be a simple, efficient, and safe therapeutic strategy for PD in the future.
- URI
- https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(17)30374-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671117303740%3Fshowall%3Dtruehttps://repository.hanyang.ac.kr/handle/20.500.11754/115883
- ISSN
- 2213-6711
- DOI
- 10.1016/j.stemcr.2017.08.017
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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