To Become or Not to Become Tumorigenic: Subventricular Zone Versus Hippocampal Neural Stem Cells.

Neural stem cells (NSCs) persist in the adult mammalian brain in two neurogenic regions: the subventricular zone lining the lateral ventricles and the dentate gyrus of the hippocampus. Compelling evidence suggests that NSCs of the subventricular zone could be the cell type of origin of glioblastoma, the most devastating brain tumor. Studies in glioblastoma patients revealed that NSCs of the tumor-free subventricular zone, harbor cancer-driver mutations that were found in the tumor cells but were not present in normal cortical tissue. Endogenous mutagenesis can also take place in hippocampal NSCs. However, to date, no conclusive studies have linked hippocampal mutations with glioblastoma development. In addition, glioblastoma cells often invade or are closely located to the subventricular zone, whereas they do not tend to infiltrate into the hippocampus. In this review we will analyze possible causes by which subventricular zone NSCs might be more susceptible to malignant transformation than their hippocampal counterparts. Cellular and molecular differences between the two neurogenic niches, as well as genotypic and phenotypic characteristics of their respective NSCs will be discussed regarding why the cell type originating glioblastoma brain tumors has been linked mainly to subventricular zone, but not to hippocampal NSCs.

Muscle Progenitors Derived from Extraocular Muscles Express Higher Levels of Neurotrophins and their Receptors than other Cranial and Limb Muscles.

Extraocular muscles (EOMs) show resistance to muscle dystrophies and sarcopenia. It has been recently demonstrated that they are endowed with different types of myogenic cells, all of which present an outstanding regenerative potential. Neurotrophins are important modulators of myogenic regeneration and act promoting myoblast proliferation, enhancing myogenic fusion rates and protecting myotubes from inflammatory stimuli. Here, we adapted the pre-plate cell isolation technique to obtain myogenic progenitors from the rat EOMs, and quantified their in vitro expression of neurotrophins and their receptors by RT-qPCR and immunohistochemistry, respectively. The results were compared with the expression on progenitors isolated from buccinator, tongue and limb muscles. Our quantitative analysis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) transcripts showed, for the first time, that EOMs-derived cells express more of these factors and that they expressed TrkA, but not TrkB and TrkC receptors. On the contrary, the immunofluorescence analysis demonstrated high expression of p75NTR on all myogenic progenitors, with the EOMs-derived cells showing higher expression. Taken together, these results suggest that the intrinsic trophic differences between EOMs-derived myogenic progenitors and their counterparts from other muscles could explain why those cells show higher proliferative and fusion rates, as well as better regenerative properties.