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 - 抽象 这个良性泌尿科跨学科研究发展中心的目标是 贝丝以色列的世界一流神经科学家和良性泌尿科研究人员在一起 执事医疗中心将集体开展科学项目，发展一个教育 外展计划并建立一个中心网站，以便为泌尿科提供宝贵的资源 社区。科学项目将使用最先进的技术，单细胞RNA-seq（SCRNA-SEQ）， 从庞蒂in尿素进行数千个神经元的同时转录组分析 中心 - 核心层（PMC-LC）和腹外侧灰灰色（PAGVL）脑区域。这些 大脑区域在控制膀胱填充和空隙中起着至关重要的作用。产生的RNA表达 轮廓将在这两个关键区域中识别神经元亚群。确定其中哪一个 亚种群最参与控制项目的膀胱：1。确定哪个 从PMC-LC到骨绳和接收PAGVL输入以及哪个PAGVL神经元的亚群项目 项目将用于PMC-LC并接收骨绳输入。 2。确定哪些亚群会改变其RNA 响应多尿模型的表达模式。神经元亚群最有可能控制 膀胱将通过开发鼠标线来研究，这些小鼠系在其中有选择地表达CRE重组酶， 允许我们定义其在正常小鼠和膀胱功能障碍中的功能作用（例如 脑退化或前列腺诱导的慢性尿道阻塞）。中心将补充并 通过参与所有团队成员的专业知识来利用科学项目 旨在增强良性泌尿科疾病研究的概况和理解的努力。这 科学努力将由1）一个活跃的研讨会计划补充 2）每年在以URO为中心的项目中对1-2个夏季研究的培训，3）定期 预定的内部中心“实验室”会议，供主要人员向整个人提供进度/问题 小组，4）一年级资金的第一年结束后，中心调查员和5） Day Long研讨会标题为“ New Frontiers in Neurourology in Neurourology”，均以BIDMC中心参与者为特色， 其他哈佛神经科学家和至少一位受邀的外部主题演讲者将在 资金第二年底。撤退和盖石研讨会将广泛地宣传给良性 泌尿科研究界。所有这些研究和教育计划都将在广告上做广告和 可以通过中心网站广泛访问，由行政核心主管构建和运行。 该网站最终将托管一个互动策划的神经图集和转录组数据库 解释性材料，可供更广泛的社区利用和下载。这个资源将 允许针对许多良性泌尿科疾病的神经基础进行针对性研究。