A novel platform to enhance single cell interrogation of nervous system development

增强神经系统发育单细胞询问的新平台

• 批准号: 10757179
• 负责人: PAUL KULESA
• 金额: $ 19.56万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-23 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10757179
• 关键词: novel; platform; enhance; single; cell

Project Summary During development, the vast majority of the peripheral nervous system (PNS) is generated from neural crest cells that migrate extensively into the embryo and give rise to the sympathetic, parasympathetic, sensory and enteric nervous systems. Sympathetic nervous system (SNS) function is tightly linked to heart rate, blood pressure and temperature control. During development the sympathetic ganglia (SG) must move and interact with axons that project from preganglionic neurons (PGNs) in the ventral spinal cord to wire the circuit between the central nervous system (CNS) and PNS. Tissue repair or regeneration therapies for birth defective or damaged neural connections between the CNS and SNS offer a potential therapeutic strategy, however, will require the molecular signature of PGN and SG cell populations prior to clinical translation. Furthermore, one clinically significant example of mistakes in SNS development is neuroblastoma cancer in infants. Here, we explore an innovative strategy of novel spatial transcriptomics approaches, integrated multiplexed RNA/protein detection and visualization, and computational algorithms to uniquely identify and map molecular markers of the PGN and SG progenitor cell populations to the tissue architecture of the chick trunk anatomy. If successful, this novel platform will provide a transformative foundation for basic research of peripheral nervous system birth defects and repair using stem cell-based therapies, and future studies of neuroblastoma initiation.

项目摘要 在开发过程中，绝大多数周围神经系统（PN）是由神经rest产生的 广泛迁移到胚胎并引起交感神经，副交感神经，感觉和 肠神经系统。交感神经系统（SNS）功能与心率，血液紧密相关 压力和温度控制。在开发过程中，交感神经神经节（SG）必须移动并相互作用 轴突从腹侧脊髓中的前神经神经元（PGNS）发射的轴突，以连接电路 中枢神经系统（CNS）和PNS。组织修复或再生疗法的出生缺陷或 CNS和SNS之间受损的神经联系会提供潜在的治疗策略，但是 在临床翻译之前，需要PGN和SG细胞群的分子特征。此外，一个 SNS发育中错误的临床意义例子是婴儿的神经母细胞瘤癌。在这里，我们 探索一种新型空间转录组学方法的创新策略，集成的多重RNA/蛋白 检测和可视化以及计算算法以唯一识别和绘制的分子标记 PGN和SG祖细胞细胞群体到雏鸡躯干解剖结构的组织结构。如果成功，这 新颖平台将为周围神经系统的基础研究提供转型基础 使用基于干细胞的疗法以及神经母细胞瘤启动的未来研究的缺陷和修复。