Maintenance and differentiation of neural stem cells

Focus Article

Alysson R. Muotri, Karina Griesi‐Oliveira, Cassiano Carromeu, Katlin B. Massirer

Published Online: Dec 16 2010

DOI: 10.1002/wsbm.100

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Abstract The adult mammalian brain contains self‐renewable, multipotent neural stem cells (NSCs) that are responsible for neurogenesis and plasticity in specific regions of the adult brain. Extracellular matrix, vasculature, glial cells, and other neurons are components of the niche where NSCs are located. This surrounding environment is the source of extrinsic signals that instruct NSCs to either self‐renew or differentiate. Additionally, factors such as the intracellular epigenetics state and retrotransposition events can influence the decision of NSC's fate into neurons or glia. Extrinsic and intrinsic factors form an intricate signaling network, which is not completely understood. These factors altogether reflect a few of the key players characterized so far in the new field of NSC research and are covered in this review. WIREs Syst Biol Med 2011 3 107–114 DOI: 10.1002/wsbm.100 This article is categorized under: Developmental Biology > Stem Cell Biology and Regeneration

Retrotransposition activation during neuronal differentiation. Long interspersed nuclear elements 1 (L1) are inhibited in neural stem cells by condensed chromatin and Sox2/histone deacetylase 1 repression. During neuronal differentiation, the chromatin is remodeled from a repressed to an activated state. At this stage, Wnt released from astrocytes stimulate the TCF/LEF (T/C) translocation from the cytoplasm to the nucleus. TCF/LEF‐binding sites overlap with Sox2‐binding sites in several genomic regions, including the promoter region of L1s. As a consequence of L1 expression, de novo integrations can occur in different genomic regions and potentially affect target gene expression.

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Signaling network regulating neural stem cell (NSC) self‐renewal and the decision on cell fate. Dynamics between extrinsic and intrinsic signals defines the NSC's self‐renewal or differentiation state.

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Combinatorial influence of niche factors and epigenetics in the decision on neuronal fate. Neural stem cells (NSC) from the subventricular zone committed to becoming neurons express the Ascl1 gene (a). On the contrary, NSCs from the subgranular zone (SGZ) show low Ascl1 expression (b). In vivo overexpression of Ascl1 in the same SGZ cells leads to an oligodendrogenesis (b). However, overexpression of Ascl1 in NSCs from SGZ, cultured in vitro, leads to neuronal fate (c).

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