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. 2012 May 18:3:81.
doi: 10.3389/fgene.2012.00081. eCollection 2012.

The genetic and epigenetic journey of embryonic stem cells into mature neural cells

Brendan M Olynik  1 , Mojgan Rastegar
Affiliations

The genetic and epigenetic journey of embryonic stem cells into mature neural cells

Brendan M Olynik et al. Front Genet. .

Abstract

Epigenetic changes occur throughout life from embryonic development into adulthood. This results in the timely expression of developmentally important genes, determining the morphology and identity of different cell types and tissues within the body. Epigenetics regulate gene expression and cellular morphology through multiple mechanisms without alteration in the underlying DNA sequences. Different epigenetic mechanisms include chromatin condensation, post-translational modification of histone proteins, DNA cytosine marks, and the activity of non-coding RNA molecules. Epigenetics play key roles in development, stem cell differentiation, and have high impact in human disease. In this review, we will discuss our current knowledge about these epigenetic mechanisms, with a focus on histone and DNA marks. We will then talk about the genetics and epigenetics of embryonic stem cell self-renewal and differentiation into neural stem cells, and further into specific neuronal cell types.

Keywords: embryonic stem cells; epigenetics; gliogenesis; homeobox transcription factors; neural stem cells; neurogenesis; regenerative medicine.

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Figures

Figure 1
Figure 1
Pathway of pluripotent stem cells to neural cell populations. Fertilization and subsequent cellular divisions create the embryonic blastocyst, where pluripotent ESC are derived (from the inner cell mass; ICM). Additionally, pluripotent and multipotent-like cells can be created via transduction of various factors into differentiated tissue, such as fibroblasts. In vitro analyses of pluripotent and multipotent neural stem cells are integral for understanding aspects of neural differentiation. The in vivo niche of stem cells contains a considerable diversity of biomolecules whose roles still need be deciphered. Exposure of ESC in vitro to various growth factors in serum free media such as fibroblast growth factor 2 (FGF2) and epithelial growth factor (EGF) allows selection of cell lines possessing a neural fate. Neural stem cells can also be acquired from adult tissue and expanded in vitro.
Figure 2
Figure 2
Behavior of neural stem cells (NSC) throughout forebrain development. Early during development, NSC increase their population of stem cells through symmetrical cell divisions. At mid-gestation, at the “neurogenic phase,” NSC divide asymmetrically, yielding a NSC and a neuron or neural progenitor cell and neuron. Neural progenitor cells can further divide symmetrically to produce two neurons. During the “gliogenic phase” in late gestation, populations of not only neurons, but astrocytes and oligodendrocytes are created (Merkle and Alvarez-Buylla, 2006).
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