☆ 4.7 Article

Folic acid stimulation of neural stem cell proliferation is associated with altered methylation profile of PI3K/Akt/CREB

JOURNAL OF NUTRITIONAL BIOCHEMISTRY (2014)

期刊

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

卷 25, 期 4, 页码 496-502

出版社

ELSEVIER SCIENCE INC

DOI: 10.1016/j.jnutbio.2013.12.010

关键词

Folic acid; DNA methylation; Neural stem cells; PI3K/Akt pathway; Proliferation

类别

Biochemistry & Molecular Biology Nutrition & Dietetics

资金

National Natural Science Foundation of China [81072289, 81130053, 81273056]
Science and Technology Development Project for Universities in Tianjin of China
Tianjin Education Commission [20100103]

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Protocol

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摘要

Proliferation of neural stem cells (NSCs) is required for development and repair in the nervous system. NSC amplification in vitro is a necessary step towards using NSC transplantation therapy to treat neurodegenerative diseases. Folic acid (FA) has been shown to act through DNA methyltransferase to stimulate NSC proliferation. To elucidate the underlying mechanism, the effect of FA on the methylation profiles in neonatal rat NSCs was assessed by methylated DNA immunoprecipitation (MeDIP) and methylated DNA immunoprecipitation-DNA microarray (MeDIP-Chip). Differentially methylated regions (DMRs) were determined by quantitative differentially methylated regions analysis, and genes carrying at least three DMRs were selected for pathway analysis. Gene network analysis revealed links with steroid biosynthesis, fatty acid elongation and the PI3K/Akt/CREB, neuroactive ligand-receptor interaction, Jak-STAT and MAPK signaling pathways. Moreover, Akt3 acted as a hub in the network, in which 14 differentially methylated genes converged to the PI3K/Akt/CREB signaling pathway. These findings indicate that FA stimulates NSC proliferation by modifying DNA methylation levels in the PI3K/Akt/CREB pathway. (C) 2014 Elsevier Inc. All rights reserved.

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