scholarly journals Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain

2021 ◽  
Author(s):  
Jayshree Samanta ◽  
James L. Salzer

ABSTRACTIn the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they regenerate oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet to induce widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jayshree Samanta ◽  
Hernandez Moura Silva ◽  
Juan J. Lafaille ◽  
James L. Salzer

AbstractIn the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they generate new oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet which induces widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.


2006 ◽  
Vol 16 (suppl_1) ◽  
pp. i103-i111 ◽  
Author(s):  
B. Seri ◽  
D.G. Herrera ◽  
A. Gritti ◽  
S. Ferron ◽  
L. Collado ◽  
...  

2014 ◽  
Vol 2 (6) ◽  
pp. 810-824 ◽  
Author(s):  
Nadia Sachewsky ◽  
Rachel Leeder ◽  
Wenjun Xu ◽  
Keeley L. Rose ◽  
Fenggang Yu ◽  
...  

2000 ◽  
Vol 16 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Francisco Javier Rubio ◽  
Carlos Bueno ◽  
Ana Villa ◽  
Beatriz Navarro ◽  
Alberto Martı́nez-Serrano

2021 ◽  
Author(s):  
Daniel Z Radecki ◽  
Albert R Wang ◽  
Abigail S Johnson ◽  
Christian A Overman ◽  
Madison M Thatcher ◽  
...  

Gli1 expressing neural stem cells, in the subventricular zone of the adult mammalian brain, respond to demyelination injury by differentiating into oligodendrocytes. We have identified Gpnmb as a novel regulator of oligodendrogenesis in Gli1 neural stem cells, whose expression is induced by TGFβ1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGFβ1 pathway by increasing the expression of the TGFβ1 binding receptor subunit, TGFβR2. Thus the TGFβ1→Gli1→Gpnmb→TGFβR2 signaling pathway forms a feed forward loop for sustained activation of TGFβ1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.


Science ◽  
2017 ◽  
Vol 356 (6345) ◽  
pp. 1383-1386 ◽  
Author(s):  
Alex Paul ◽  
Zayna Chaker ◽  
Fiona Doetsch

Neural stem cells (NSCs) in specialized niches in the adult mammalian brain generate neurons throughout life. NSCs in the adult mouse ventricular-subventricular zone (V-SVZ) exhibit a regional identity and, depending on their location, generate distinct olfactory bulb interneuron subtypes. Here, we show that the hypothalamus, a brain area regulating physiological states, provides long-range regionalized input to the V-SVZ niche and can regulate specific NSC subpopulations. Hypothalamic proopiomelanocortin neurons selectively innervate the anterior ventral V-SVZ and promote the proliferation of Nkx2.1+ NSCs and the generation of deep granule neurons. Accordingly, hunger and satiety regulate adult neurogenesis by modulating the activity of this hypothalamic–V-SVZ connection. Our findings reveal that neural circuitry, via mosaic innervation of the V-SVZ, can recruit distinct NSC pools, allowing on-demand neurogenesis in response to physiology and environmental signals.


Development ◽  
2019 ◽  
Vol 146 (4) ◽  
pp. dev156059 ◽  
Author(s):  
Kirsten Obernier ◽  
Arturo Alvarez-Buylla

2020 ◽  
Vol 10 ◽  
Author(s):  
Ángela Fontán-Lozano ◽  
Sara Morcuende ◽  
Mª América Davis-López de Carrizosa ◽  
Beatriz Benítez-Temiño ◽  
Rebeca Mejías ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document