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: 10678917
• 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/10678917
• 关键词: Acceleration; Address; Advanced Development; Age; Algorithms; Anatomy; Architecture; Atlases; Axon; Basic Science; Biological Assay; Birth; Blood Pressure; Cells; Cellular Structures; Central Nervous System; Chick; Clinical Research; Computational algorithm; Computer software; Congenital Abnormality; Data; Detection; Development; Embryo; Enteric Nervous System; Fiji; Fluorescence; Foundations; Future; Gene Expression; Gene Expression Profiling; Gene Targeting; Genes; Genetic Transcription; Genomics; Goals; Heart Rate; Imaging Device; Immunohistochemistry; Infant; Link; Location; Malignant Neoplasms; Maps; Methods; Molecular; Molecular Profiling; Nervous System Physiology; Neural Crest Cell; Neuroblastoma; Neurons; Organism; Patients; Peripheral; Peripheral Nervous System; Population; Proteins; Pythons; Qualifying; Quality of life; RNA; Research; Resolution; Sensory; Spinal Cord; Structure; Sympathetic Ganglia; Sympathetic Nervous System; System; Technology; Temperature; Therapeutic; Tissues; Validation; Visualization; candidate validation; cell motility; clinical translation; clinically significant; computerized tools; ganglion cell; improved; innovation; model organism; molecular marker; nervous system development; neural; neural repair; novel; novel marker; novel strategies; preservation; progenitor; protein expression; regenerative therapy; repair strategy; repaired; single cell technology; single-cell RNA sequencing; software development; spatial integration; stem cell therapy; stem cells; tissue regeneration; tissue repair; tool; transcriptomics

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 在发育过程中，绝大多数周围神经系统（PNS）是由神经嵴产生的 细胞广泛迁移到胚胎中，并产生交感神经，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 压力和温度控制。在发育过程中，交感神经节（SG）必须移动和相互作用 从腹侧脊髓中的节前神经元（PGNs）伸出的轴突将回路连接在 中枢神经系统（CNS）和PNS。组织修复或再生治疗出生缺陷或 然而，CNS和SNS之间的神经连接受损提供了一种潜在的治疗策略， 需要PGN和SG细胞群的分子标记，然后才能进行临床转化。此外，一 SNS发展中的错误的临床上重要的例子是婴儿的神经母细胞瘤癌症。这里我们 探索新的空间转录组学方法的创新策略，整合多重RNA/蛋白质 检测和可视化，以及计算算法，以唯一地识别和映射的分子标记物， PGN和SG祖细胞群与鸡躯干解剖学的组织结构的关系。如果成功，这 一个新的平台将为周围神经系统出生的基础研究提供变革性的基础 缺陷和修复使用干细胞为基础的治疗，以及未来的研究神经母细胞瘤的启动。