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NTPDase2 and Purinergic Signaling Control Progenitor Cell Proliferation in Neurogenic Niches of the Adult Mouse Brain
- Source :
- Stem Cells
- Publication Year :
- 2015
-
Abstract
- Nerve cells are continuously generated from stem cells in the adult mammalian subventricular zone (SVZ) and hippocampal dentate gyrus. We have previously noted that stem/progenitor cells in the SVZ and the subgranular layer (SGL) of the dentate gyrus express high levels of plasma membrane-bound nucleoside triphosphate diphosphohydrolase 2 (NTPDase2), an ectoenzyme that hydrolyzes extracellular nucleoside diphosphates and triphosphates. We inferred that deletion of NTPDase2 would increase local extracellular nucleoside triphosphate concentrations perturbing purinergic signaling and boosting progenitor cell proliferation and neurogenesis. Using newly generated mice globally null for Entpd2, we demonstrate that NTPDase2 is the major ectonucleotidase in these progenitor cell-rich areas. Using BrdU-labeling protocols, we have measured stem cell proliferation and determined long-term survival of cell progeny under basal conditions. Brains of Entpd2 null mice revealed increased progenitor cell proliferation in both the SVZ and the SGL. However, this occurred without noteworthy alterations in long-term progeny survival. The hippocampal stem cell pool and the pool of the intermediate progenitor type-2 cells clearly expanded. However, substantive proportions of these proliferating cells were lost during expansion at around type-3 stage. Cell loss was paralleled by decreases in cAMP response element-binding protein phosphorylation in the doublecortin-positive progenitor cell population and by an increase in labeling for activated caspase-3 levels. We propose that NTPDase2 has functionality in scavenging mitogenic extracellular nucleoside triphosphates in neurogenic niches of the adult brain, thereby acting as a homeostatic regulator of nucleotide-mediated neural progenitor cell proliferation and expansion. Stem Cells 2015;33:253–264
- Subjects :
- Neurogenesis
Subventricular zone
Biology
Article
Mice
Neural Stem Cells
medicine
Animals
Progenitor cell
Stem Cell Niche
Progenitor
Cell Proliferation
Adenosine Triphosphatases
Brain
Cell Biology
Immunohistochemistry
Neural stem cell
Cell biology
Endothelial stem cell
medicine.anatomical_structure
Immunology
Molecular Medicine
Stem cell
Developmental Biology
Adult stem cell
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Stem Cells
- Accession number :
- edsair.doi.dedup.....126f35bdcf84fa7c975421044189891d