Abstract
Among the regulatory mechanisms of the renewal and differentiation of neural stem cells, recent evidences support that epigenetic modifications such as DNA methylation, histone modification, and noncoding RNAs play critical roles in the regulation on the proliferation and differentiation of neural stem cells. In this review, we discussed recent advances of DNA modifications on the regulative mechanisms of neural stem cells. Among these epigenetic modifications, DNA 5-hydroxymethylcytosine (5hmC) modification is emerging as an important modulator on the proliferation and differentiation of neural stem cells. At the same time, Ten-eleven translocation (Tet) methylcytosine dioxygenases, the rate-limiting enzyme for the 5-hydroxymethylation reaction from 5-methylcytosine to 5-hydroxymethylcytosine, play a critical role in the tumorigenesis and the proliferation and differentiation of stem cells. The functions of 5hmC and TET proteins on neural stem cells and their roles in neurological diseases are discussed.
Highlights
Human beings are developed from a fertilized egg into a complete individual; during the whole process, a series of precise regulations on the development are included, such as gene expression and gene silence [1], transcriptional regulation [2], posttranscriptional regulation [3], hormone regulation [4], chromosome behavior regulation [5], and apoptosis [6]
Reynolds and Weiss first found that the neurons isolated from the striatum of the adult mouse brain could proliferate and differentiate in vitro with epidermal growth factors [9], indicating the existence of neural stem cells (NSCs) in the mature nervous system
The renewal and differentiation ability of NSC is limited; in the process of aging or pathological conditions, neuronal cell loss is much more than newly generated neurons and glial cells from NSCs, resulting in different neurological disorders including Alzheimer’s disease [10], Parkinson’s disease [11], Huntington’s disease [12], neuroendocrine tumors [13], and ataxia [14]
Summary
Human beings are developed from a fertilized egg into a complete individual; during the whole process, a series of precise regulations on the development are included, such as gene expression and gene silence [1], transcriptional regulation [2], posttranscriptional regulation [3], hormone regulation [4], chromosome behavior regulation [5], and apoptosis [6] For these different regulative pathways, their target cells are embryonic stem cells (ESCs). Reynolds and Weiss first found that the neurons isolated from the striatum of the adult mouse brain could proliferate and differentiate in vitro with epidermal growth factors [9], indicating the existence of neural stem cells (NSCs) in the mature nervous system They demonstrated that NSC has the ability to self-renew and differentiate into other types of cells like neurons, astrocytes, and oligodendrocytes under many conditions such as growth factors, neurotransmitters, hormones, injury, or environmental factors [9]. We will review the recent advances of different epigenetic modifications on NSCs, but mainly focus on the role of 5hmC as a new player in the regulation of the renewal and differentiation of ESCs or NSCs
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