Peripheral neural stem cells - maintenance in peripheral ganglia and nerves

周围神经干细胞 - 维持周围神经节和神经

• 批准号: 5377743
• 负责人: Professor Dr. Hermann Rohrer
• 金额: --
• 依托单位: Abteilung Neurochemie (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5377743?language=en
• 关键词: Peripheral; neural; stem; cells; maintenance

We use the neural crest as a model system to study the biology of vertebrate neural stem cells. Stem cells are present in neural crest and in neural crest-derived peripheral ganglia and nerves. Peripheral nerve stem cells (called here PNSCs) were induced to differentiate in vivo to noradrenergic sympathetic neurons in response to differentiation factors (BMPs) and transcription factors (Cash1, Phox2a, Phox2b, dHand) involved in autonomic neuron development. The neurogenin bHLH transcription factors directed the differentiation to sensory neurons. However, the number of cells generated was small and the PNSCs were identified retrospectively by the differentiation of their progeny. Recently, PNSCs were prospectively isolated and were shown to be self-renewing and to give rise to neuronal and glial cells in clonal cultures. However, when isolated PNSCs were transplanted into the PNS of host embryos they gave rise to neurons that did neither express noradrenergic nor sensory properties. This project aims to overcome this restriction and to elicit the generation of noradrenergic and sensory neurons from isolated PNSCs. We propose to develop stem cell culture conditions for PNSCs, to analyse the developmental potential of PNSCs in vitro and by transplantation into early host embryos. We will investigate the effect of stem cell propagation in culture on the potential to develop noradrenergic and sensory neuronal fates in vivo and to express specific transcription factors in immunoselected, cultured PNSCs to induce the generation of noradrenergic and sensory neurons.

我们使用神经脊作为模型系统来研究脊椎动物神经干细胞的生物学。干细胞存在于神经脊以及神经脊衍生的外周神经节和神经中。周围神经干细胞(PNSCs)在自主神经发育相关的分化因子(BMPs)和转录因子(Cash1、Phox2a、PHOX2B、DHand)的作用下，在体内被诱导分化为去甲肾上腺素能交感神经元。神经原bHLH转录因子引导感觉神经元分化。然而，PNSCs的生成数量很少，并通过其后代的分化进行了回顾性鉴定。最近，PNSCs被前瞻性地分离出来，并被证明具有自我更新能力，并在克隆培养中分化为神经元和神经胶质细胞。然而，当分离的PNSCs被移植到宿主胚胎的PNS中时，它们产生的神经元既不表达去甲肾上腺素，也不表达感觉特性。该项目旨在克服这一限制，并诱导从分离的PNSCs产生去甲肾上腺素能神经元和感觉神经元。我们建议建立PNSCs的干细胞培养条件，分析PNSCs在体外的发育潜力，并通过移植到早期宿主胚胎中。我们将研究干细胞在培养中的繁殖对体内去甲肾上腺素能和感觉神经元命运的影响，并在免疫选择的培养的PNSCs中表达特定的转录因子，以诱导去甲肾上腺素和感觉神经元的产生。