Epigenetic regulation in neural stem cell differentiation

Abstract

The central nervous system (CNS) is composed of three major cell types -neurons, astrocytes, and oligodendrocytes -which differentiate from common multipotent neural stem cells (NSCs). This differentiation process is regulated spatiotemporally during the course of mammalian development. It is becoming apparent that epigenetic regulation is an important cell-intrinsic program, which can interact with transcription factors and environmental cues to modulate the differentiation of NSCs. This knowledge is important given the potential of NSCs to produce specific CNS cell types that will be beneficial for clinical applications. Here we review recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NSC fate during CNS development, with a particular focus on the developing mammalian forebrain.

Epigenetics of Neural Repair Following Spinal Cord Injury

“…In considering how to manipulate chromatin to better stimulate adult neural stem cells (NSC) to participate in endogenous repair, or to control stem cells prior to or after SCI transplantation, it is important to understand how the chromatin state of NSCs in adult differs from those in the embryo [149]. This may be particularly important in the spinal cord, where our understanding of adult progenitor subtypes lags far behind that in the adult brain [150].…”

Two novel aspects of the kinetics of gene expression including miRNAs

“…The mRNA-proteinmediated spontaneous differentiation occurring with a certain probability can be described taking stochasticity into account [45] More recent experimental studies indicate that the differentiation of stem cells often involves the changes in gene transcription into miRNAs and/or interplay between mRNAs and miRNAs (reviewed in Refs. [50][51][52][53]). The advantage of miRNAs is that they often have many target mRNAs, and accordingly the change of the rate of formation of one of miRNAs may result in appreciable changes in the populations of many mRNAs and corresponding proteins.…”

Neuroinflammation on the Epigenetics of Neural Stem Cells

“…First, methylation of CpG dinucleotides affects DNA structure and can directly interfere with the binding of TFs to their target sequences (Takizawa et al, 2001); second, a more pervasive effect, methyl-CpG-binding domain (MBD)-containing protein family members can bind to genes with methylated CpG dinucleotides, thereby suppressing the genes' expression (Nan et al, 1997) Though, DNA methylation is actively involved in the acquisition of multipotentiality in NSC from early-, mid-to late-gestation. Here, we mainly focus on two well-studied pathways that act synergistically to promote astrocytic differentiation of NSC are those activated by the interleukin-6 (IL-6) family of cytokines such as leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and cardiotrophin-1 (CT-1) and bone morphogenetic protein (BMP) signaling (Juliandi et al, 2010). In early-and mid-gestational NSCs, astrocytic gene promoters such as glial fibrillary acidic protein (GFAP) are hypermethylated, a status that impedes binding of the STAT3-p300 ⁄CBP-SMADs complex to its target sequence and thus prevents these NSCs from differentiating into astrocytes even when the cells are stimulated by astrocyte-inducing cytokines (Takizawa et al, 2001).…”