Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease | Zendy

Noviana Wulansari | Zendy; Eun Hee Kim | Zendy; Yanuar Alan Sulistio | Zendy; Yong-Hee Rhee | Zendy; Jae J. Song | Zendy; SangHun Lee | Zendy

Open Access

Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease

Author(s) -

Noviana Wulansari,

Eun Hee Kim,

Yanuar Alan Sulistio,

Yong-Hee Rhee,

Jae J. Song,

SangHun Lee

Publication year - 2017

Publication title -

stem cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.207

H-Index - 76

ISSN - 2213-6711

DOI - 10.1016/j.stemcr.2017.08.017

Subject(s) - biology , epigenetics , midbrain , neural stem cell , transplantation , dna methylation , neuron , stem cell , cancer research , microbiology and biotechnology , gene , neuroscience , gene expression , medicine , central nervous system , genetics

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

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