Purinergic signaling regulates neural progenitor cell expansion and neurogenesis
Purinergic signaling regulates neural progenitor cell expansion and neurogenesis
复制标题
DOI：
10.1016/j.ydbio.2006.09.017
复制
发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
--
作者：
Lin, Jane H. -C.;Takano, Takahiro;Nedergaard, Maiken
神经干细胞和祖细胞通常表现出密度依赖性的存活和扩增，使得需要临界密度，低于该临界密度，克隆原祖细胞丢失。这表明，短距离自分泌因子可能是至关重要的祖细胞的维护。我们在这里报告说，嘌呤驱动脑室区神经干细胞和祖细胞的扩张，嘌呤受体激活是祖细胞维持原样所必需的。神经祖细胞表达P2Y嘌呤受体，并动员细胞内钙响应激动剂。受体拮抗剂抑制增殖，并允许分化成神经元和神经胶质细胞在体外，而随后去除嘌呤抑制恢复祖细胞扩增。细胞外ATP的实时生物发光成像显示，细胞外核苷酸的来源是祖细胞本身，其似乎在突发事件中释放ATP。酶组织化学的成年大鼠大脑的外核苷酸酶活性显示，NTDt3，其作用是降解活性ATP，从而清除它从活跃的嘌呤能传输的地区，被选择性地定位到脑室下区和齿状回，在该地区的神经元分化的祖细胞池的收益。这些数据表明，嘌呤核苷酸作为神经前体细胞的增殖信号，从而作为终端神经元分化的负调节剂。因此，祖细胞衍生的神经发生因此与活性嘌呤能信号传导及其调节的区域相关（c）2006 Elsevier Inc. All rights reserved.
Neural stem and progenitor cells typically exhibit a density-dependent survival and expansion, such that critical densities are required below which clonogenic progenitors are lost. This suggests that short-range autocrine factors may be critical for progenitor cell maintenance. We report here that purines drive the expansion of ventricular zone neural stem and progenitor cells, and that purine receptor activation is required for progenitor cells to be maintained as such. Neural progenitors expressed P2Y purinergic receptors and mobilized intracellular calcium in response to agonist. Receptor antagonists suppressed proliferation and permitted differentiation into neurons and glia in vitro, while subsequent removal of purinergic inhibition restored progenitor cell expansion. Real-time bioluminescence imaging of extracellular ATP revealed that the source of extracellular nucleotides are the progenitor cells themselves, which appear to release ATP in episodic burst events. Enzyme histochemistry of the adult rat brain for ectonucleotidase activity revealed that NTDPase, which acts to degrade active ATP and thereby clears it from areas of active purinergic transmission, was selectively localized to the subventricular zone and the dentate gyrus, regions in which neuronal differentiation proceeds from the progenitor cell pool. These data suggest that purine nucleotides act as proliferation signals for neural progenitor cells, and thereby serve as negative regulators of terminal neuronal differentiation. As a result, progenitor cell-derived neurogenesis is thus associated with regions of both active purinergic signaling and modulation thereof (c) 2006 Elsevier Inc. All rights reserved.