Journal
STEM CELLS
Volume 36, Issue 10, Pages 1578-1588Publisher
WILEY
DOI: 10.1002/stem.2886
Keywords
Vitamin C; Neural stem cell; Astrocyte; DNA methylation; DNA hydroxymethylation
Categories
Funding
- collaborative genome program for fostering new post-genome industry of the National Research Foundation (NRF) - Ministry of Science and ICT (MSIT) [NRF-2014M3C9A3068554, NRF-2017MBA9B5060884, NRF-2017M3C9A5028693, 2017R1A5A2015395, NRF-2017R1A2B2002220]
- Korea Research Institute of Bioscience and Biotechnology Research Initiative grant
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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.
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