Single cell transcriptome profiling to define cell types in brain nuclei controlling bladder function

单细胞转录组分析可定义控制膀胱功能的脑核细胞类型

• 批准号: 9788435
• 负责人: Mark L. Zeidel
• 金额: $ 35万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788435
• 关键词: Affect; Alzheimer' s Disease; Atlases; Benign; Bladder; Bladder Control; Bladder Diseases; Bladder Dysfunction; Brain; Brain region; Caring; Cell Nucleus; Cells; Chronic; Collaborations; Communities; Data; Databases; Development; Disease; Enterobacteria phage P1 Cre recombinase; Expression Profiling; Funding; Gene Expression; Genetic; Genetic Transcription; Goals; Human Resources; Individual; Institutes; Interdisciplinary Study; Internet; Investigation; Israel; Knowledge; Medical center; Modeling; Monitor; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Neurons; Participant; Pattern; Physicians; Play; Polyuria; Pontine structure; Process; Prostate; Reporting; Research; Research Personnel; Resources; Role; Running; Schedule; Scientist; Techniques; Training; Traumatic Brain Injury; Urethral Obstruction; Urination; Urologic Diseases; Urology; Work; cell type; design; frontier; insight; interest; locus ceruleus structure; meetings; member; midbrain central gray substance; outreach; outreach program; programs; relating to nervous system; response; selective expression; single-cell RNA sequencing; summer research; symposium; transcriptome; undergraduate student; urologic; web site

Overall - Abstract The goal of this Developmental Center for Interdisciplinary Research in Benign Urology is to bring together a team of world-class neuroscientists and benign urology researchers at the Beth Israel Deaconess Medical Center who will collectively undertake a scientific project, develop an educational outreach program and build a Center website in order to provide an invaluable resource for the urology community. The scientific project will use a state of the art technique, single cell RNA-seq (scRNA-seq), to perform simultaneous transcriptome profiling of thousands of neurons from the pontine micturition center-locus coeruleus (PMC-LC) and ventrolateral periaqueductal gray (PAGVL) brain regions. These brain regions play a critical role in controlling bladder filling and voiding. The resulting RNA expression profiles will identify the neuron subpopulations in these two crucial regions. To determine which of these subpopulations are most engaged in controlling the bladder the project will: 1. Determine which subpopulations project from PMC-LC to sacral cord and receive PAGVL input, and which PAGVL neurons project to PMC-LC and receive sacral cord input. 2. Determine which subpopulations alter their RNA expression patterns in response to a model of polyuria. Neuron subpopulations most likely to control the bladder will be studied by developing mouse lines which selectively express Cre recombinase in them, permitting us to define their functional role in normal mice and mice with disorders of bladder function (e.g. brain degeneration or prostate-induced chronic urethral obstruction). The Center will supplement and leverage the scientific project by engaging the expertise of all team members in educational outreach efforts designed to enhance the profile and understanding of benign urological disease research. The scientific efforts will be supplemented by 1) an active seminar program featuring invited outside speakers, 2) the training of 1 - 2 summer research undergraduates each year in uro-centric projects, 3) a regularly scheduled internal Center `lab' meeting for key personnel to present their progress/problems to the entire group, 4) an end-of-year retreat after the first year of funding is complete of Center investigators and 5) a day long symposium titled `New Frontiers in NeuroUrology' featuring both BIDMC Center participants, other Harvard neuroscientists and at least one invited external keynote speaker that will take place at the end of year 2 of funding. The retreat and the capstone symposium will be advertised broadly to the benign urology research community. All of these research and educational initiatives will be advertised on and made broadly accessible through a Center website to be built and run by the Administrative Core Director. This website will ultimately host an interactive curated neural atlas and transcriptome database with interpretive material, available for the broader community to utilize and download. This resource will permit targeted investigations of the neural underpinnings of numerous benign urological diseases.

总体-摘要 这个良性泌尿科跨学科研究发展中心的目标是 一个由世界级神经科学家和良性泌尿学研究人员组成的团队， 女执事医疗中心谁将集体承担一个科学项目，开发一个教育 外展计划，并建立一个中心网站，以提供一个宝贵的资源，泌尿科 社区该科学项目将使用最先进的技术，单细胞RNA-seq（scRNA-seq）， 对来自脑桥排尿的数千个神经元进行同步转录组分析 中央蓝斑（PMC-LC）和腹外侧导水管周围灰质（PAGVL）脑区。这些 大脑区域在控制膀胱充盈和排泄中起关键作用。由此产生的RNA表达 图谱将识别这两个关键区域中的神经元亚群。为了确定这些 亚群大多参与控制膀胱，该项目将：1。确定哪些 从PMC-LC投射到骶髓并接受PAGVL输入的亚群， 投射到PMC-LC并接收骶髓输入。2.确定哪些亚群改变了它们的RNA 表达模式，以响应多尿模型。神经元亚群最有可能控制 膀胱将通过开发在其中选择性表达Cre重组酶的小鼠系来研究， 使我们能够确定它们在正常小鼠和膀胱功能紊乱的小鼠中的功能作用（例如， 脑变性或前列腺引起的慢性尿道梗阻）。该中心将补充和 通过让所有团队成员的专业知识参与教育推广活动来利用科学项目 旨在提高良性泌尿系统疾病研究的概况和理解的努力。的 科学工作将得到以下补充：1）一个积极的研讨会计划，邀请外部发言人， 2)每年在以泌尿系统为中心的项目中培训1 - 2名暑期研究生，3）定期 为关键人员安排内部中心“实验室”会议，向全体人员介绍他们的进展/问题 4）在第一年的资助完成后，中心研究人员进行年终务虚会，5） 为期一天的题为“神经泌尿学新前沿”的研讨会， 其他哈佛神经科学家和至少一位受邀的外部主题演讲人，将在 第二年融资结束。务虚会和顶点研讨会将广泛宣传的良性 泌尿学研究团体。所有这些研究和教育活动将在 通过由行政核心主任建立和管理的中心网站广泛提供。 该网站最终将托管一个交互式策划的神经图谱和转录组数据库， 解释性材料，可供更广泛的社区使用和下载。此资源将 允许对许多良性泌尿系统疾病的神经基础进行有针对性的调查。