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Nucleotide receptors govern proliferation and differentiation of human neural stem cells

核苷酸受体控制人神经干细胞的增殖和分化

基本信息

批准号：
32972016
负责人：
Professor Dr. Herbert Zimmermann
金额：
--
依托单位：
Institut für Zellbiologie und Neurowissenschaft
依托单位国家：
德国
项目类别：
Research Units
财政年份：
2007
资助国家：
德国
起止时间：
2006-12-31 至 2009-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/32972016?language=en
关键词：
Nucleotide receptors govern proliferation differentiation

项目摘要

Nucleotides such as UTP and ATP, are amongst the phylogenetically and ontogentically oldest neurotransmitters. Via nucleotide receptor activation they provide mitogenic and survival signals for various cell types, including neural stem cells, astrocytes and neurons. Neural stem cells are present in the mammalian embryonic, fetal and adult brain giving rise to neurons and glia. These cells can be readily isolated, expanded and differentiated in vitro. In this project, we wish to study human tissue specific neural stem cells and as an additional model system embryonic mouse neural stem cells because 1. human neural stem cells have the highest relevance for human disease and 2. human neural stem cells maintain a high proliferative potential after many months in vitro. On the other hand, mouse neural stem cells can be obtained from genetically engineered animals offering the advantages of mouse genetics. In a first collaborative effort we showed that activation of metabotropic nucleotide receptors promotes proliferation and dopaminergic differentiation of human neural stem cells. The goal of the proposed research is to further investigate the functional expression of nucleotide receptors and their mechanistic role in affecting neural stem cell proliferation and differentiation in both human and mouse embryonic neural stem cells. The study is expected to provide novel insight and practical improvement for the effective in vitro production of neurons with a defined transmitter (e. g. dopaminergic) phenotype.

核苷酸，如UTP和ATP，是胚胎发育和个体发育中最古老的神经递质之一。通过核苷酸受体活化，它们为各种细胞类型提供促有丝分裂和存活信号，包括神经干细胞、星形胶质细胞和神经元。神经干细胞存在于哺乳动物的胚胎、胎儿和成人脑中，产生神经元和神经胶质。这些细胞可以容易地在体外分离、扩增和分化。在本项目中，我们希望研究人类组织特异性神经干细胞，并作为额外的模型系统胚胎小鼠神经干细胞，因为1。人类神经干细胞与人类疾病具有最高的相关性;人神经干细胞在体外数月后仍保持高增殖潜力。另一方面，小鼠神经干细胞可以从基因工程动物中获得，提供小鼠遗传学的优势。在第一次合作中，我们发现代谢型核苷酸受体的激活促进了人类神经干细胞的增殖和多巴胺能分化。该研究的目的是进一步研究核苷酸受体的功能表达及其在人和小鼠胚胎神经干细胞中影响神经干细胞增殖和分化的机制。该研究有望为体外有效生产具有特定递质的神经元提供新的见解和实际改进。G.多巴胺能）表型。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Distribution of ectonucleotidases in the rodent brain revisited

DOI：
10.1007/s00441-008-0681-x
发表时间：
2008-11-01
期刊：
CELL AND TISSUE RESEARCH
影响因子：
3.6
作者：
Langer, David;Hammer, Klaus;Zimmermann, Herbert
通讯作者：
Zimmermann, Herbert

Purinergic receptor activation inhibits osmotic glial cell swelling in the diabetic rat retina.

嘌呤能受体激活抑制糖尿病大鼠视网膜渗透性胶质细胞肿胀

DOI：
10.1016/j.exer.2008.07.004
发表时间：
2008
期刊：
Experimental eye research
影响因子：
3.4
作者：
Wurm A;Inandiev I;Hollborn M;Wiedemann P;Reichenbach A;Zimmermann H;Bringmann A;Pannicke T
通讯作者：
Pannicke T

Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells