Abstract
C-terminal binding proteins (CtBPs) are transcriptional modulators that can regulate gene expression through the recruitment of a corepressor complex composed of chromatin-modifying enzymes and transcriptional factors. In the brain, CtBPs have been described as regulators of cell proliferation, differentiation, and survival. Nevertheless, the role of CtBPs on postnatal neural stem cells (NSCs) fate is not known yet. Herein, we evaluate the expression and functions of CtBPs in postnatal NSCs from the subventricular zone (SVZ). We found that CtBPs were expressed in immature/progenitor cells, neurons and glial cells in the SVZ niche. Using the CtBPs modulator 4-methylthio 2-oxobutyric acid (MTOB), our results showed that 1 mM of MTOB induced cell death, while 5, 25, and 50 μM increased the number of proliferating neuroblasts, mature neurons, and oligodendrocytes. Interestingly, it also increased the dendritic complexity of immature neurons. Altogether, our results highlight CtBPs putative application for brain regenerative applications.
Highlights
Neural stem cells (NSCs) are multipotent cells that can proliferate through long-term self-renewal and differentiate into neurons and glial cells (Pino et al, 2017)
subventricular zone (SVZ) NSCs are initially grown in proliferative conditions, forming neurospheres that are enriched in progenitors and immature cells
SVZ cells were cultured under differentiation conditions for 48 h and for 7 days, followed by immunocytochemistry against CtBP1 or CtBP2 together with several markers for proliferating (Ki67) and immature cells (Nestin and Sox2), neuroblasts (DCX), neurons (NeuN and MAP2), astrocytes-like cells (GFAP), oligodendrocytes/type C cells (Olig2) and mature oligodendrocytes (MBP and PLP)
Summary
Neural stem cells (NSCs) are multipotent cells that can proliferate through long-term self-renewal and differentiate into neurons and glial cells (Pino et al, 2017). The modulation of NSCs behavior represents a promising approach for the development of potential therapeutic strategies for brain repair These cells persist in the adult mammalian brain in two main neurogenic niches, the subventricular zone (SVZ) along the walls of the lateral ventricles, and in the subgranular zone (SGZ) of the hippocampus (Garcia et al, 2004). SVZ-derived NSCs can differentiate into interneurons in the olfactory bulb and they are a source of oligodendrocytic progenitor cells that generate myelinating oligodendrocytes (Kriegstein and Alvarez-Buylla, 2009; Obernier and Alvarez-Buylla, 2019). Several intrinsic factors, such as transcriptional factors and epigenetic modifications may impact on NSC fate (Ming and Song, 2011). CtBPs are encoded by two genes, Role of CtBPs in NCSs
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