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Title 

Vitamin C promotes astrocyte differentiation through DNA hydroxymethylation

Authors 

Jong-Hwan KimMiRang KimX B HeN WulansariByoung Ha YounDong Hyuck BaeNanHyung HuhYong Sung KimS H LeeSeon-Young Kim

Publisher 

Wiley

Issue Date 

2018

Citation 

Stem Cells

Keywords 

AstrocyteDNA hydroxymethylationDNA methylationNeural stem cellVitamin C

Abstract 

Previous studies have reported that vitamin C (VC) promotes neural stem/precursor cell (NSC) differentiation toward dopamine (DA) neurons via DNA hydroxymethylation-induced transcriptional activation of DA neuron-specific genes. To further understand the VC effects on NSC differentiation, we profiled the transcriptome and DNA methylome/hydroxymethylome using high-throughput sequencing. Interestingly, RNA sequencing analyses have shown that, in addition to DA neuronal genes, astrocytic genes Gfap, Slc1a3, and S100a16 were also upregulated in NSC cultures differentiated with VC treatment. Consistently, enhanced GFAP+ astrocytic yields were manifested in the differentiated cultures with VC treatment, collectively indicating that VC promotes astrocytic differentiation. In genome-wide hydroxymethylome analyses, VC treatment induces enrichment of DNA hydroxymethylation (5-hydroxymethyl cytosine; 5hmC) near the consensus binding motifs of nuclear factor I (NFI). Furthermore, we showed that VC significantly enhanced recruitment of NFI and STAT3, key transcription factors for astrogenesis, in the 5hmC-enriched regions of the astrocyte-specific genes. These findings suggest that VC play important roles in astrocytogenesis during brain development. Stem Cells 2018; 36:1578-1588.

ISSN 

1066-5099

Link 

http://dx.doi.org/10.1002/stem.2886

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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