Molecular and fate maps of prostatic stroma

前列腺基质的分子和命运图谱

• 批准号: 9178337
• 负责人: CHAD M. VEZINA
• 金额: $ 29.79万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9178337
• 关键词: Accounting; Androgen Receptor; Antibodies; Antineoplastic Agents; Atlases; Behavior; Benign; Benign Prostatic Hypertrophy; Biology; Cell Lineage; Cells; Chad; Clinical; Communities; Complement; Complex; Data; Data Set; Databases; Daughter; Development; Disease; Drug Targeting; Drug resistance; Ductal; Epithelial; Epithelial Cells; Epithelium; Extracellular Matrix; Fibroblasts; Functional disorder; Gene Expression; Generations; Genetic; Genetic Transcription; Goals; Growth; Growth Factor Receptors; Homeostasis; Hormones; Human; Hyperplasia; Image; Inflammation; Inflammatory Response; Knowledge; Label; Link; Malignant Neoplasms; Maps; Mediating; Messenger RNA; Molecular; Mus; Muscle; Muscle Cells; Organ; Paracrine Communication; Pathogenesis; Pathway interactions; Pattern; Pericytes; Population; Positioning Attribute; Principal Investigator; Process; Proliferating; Prostate; Prostatic Diseases; Prostatic Stroma; Proteins; Publications; RNA; Research; Research Personnel; Resolution; Resources; Rodent; Role; Signal Pathway; Signal Transduction; Smooth Muscle; Smooth Muscle Myocytes; Specimen; Sphincter; Striated Muscles; Stromal Cells; Technology; Testing; Tissues; Urethra; Urology; Work; arm; base; cancer pain; cell behavior; cell type; daughter cell; design; experience; fetal; genetic approach; genetic manipulation; human data; innovation; interest; male; meetings; online tutorial; progenitor; programs; protein expression; regenerative; repaired; resistance factors; spectrograph; stromal progenitor; time use; tool; transcription factor; urinary

PROJECT SUMMARY An impressive suite of tools is available for studying prostatic epithelial cells; surprisingly few exist for prostatic stroma, even though it drives most of the prostate's significant biologic behaviors. Prostatic stroma initiates glandular development and releases paracrine signals that stimulate epithelial growth during benign hyperplasia and cancer. It also synthesizes extracellular matrix molecules that mediate regenerative repair and increase organ stiffness, factors recently associated with urinary dysfunction. Pinpointing prostatic stromal progenitors and factors involved in their proliferation and differentiation are the first steps in identifying cellular mechanisms responsible for stroma-based disease processes. Our first aim uses a mouse genetic approach to identify progenitors giving rise to prostatic fibroblasts, smooth muscle cells, perivascular cells and urinary striated muscle sphincter myocytes. We will use immunostaining and multispectral imaging to assign lineage labeled cells to two- and three—dimensional maps of prostatic stromal sub-compartments. These data will be presented using an innovative online tool that connects researchers with validated cre-expressing mouse lines and stromal- cell selective antibodies. Our second aim is to create a developing human prostatic stroma RNA and protein expression atlas to stimulate hypotheses that are relevant to prostatic disease causing behaviors of stromal progenitors identified in Aim 1. We will map expression patterns for key growth factors, receptors, and transcription factors that potentially mediate prostatic stromal and epithelial differentiation. This work complements the high-resolution developing mouse prostatic atlas we made previously for GUDMAP. Our results will be used to generate online tutorials of prostate development and we will identify homologous compartments between mouse and human. We will annotate human data when possible with the same terms used previously to annotate mouse data, providing a searchable online dataset which enables investigators to compare RNA/protein expression between mouse and human and identify conserved pathways across species. Our data will equip the prostate research community with the necessary tools to design and test new hypotheses about the pathogenic role of prostatic stroma in benign hyperplasia, inflammation, pain, and cancer.

项目摘要 一套令人印象深刻的工具可用于研究前列腺上皮细胞。令人惊讶的是很少有 前列腺基质，即使它驱动了前列腺大部分重要的生物学行为。前列腺基质 启动腺发育并释放旁分泌信号，以刺激良性期间上皮生长 增生和癌症。它还综合了细胞外基质分子，这些分子是介质再生修复和 增加器官刚度，最近与尿功能障碍相关的因素。精确指出前列腺基质 祖细胞和涉及其增殖和分化的因素是识别细胞的第一步 负责基于基质的疾病过程的机制。我们的第一个目标使用鼠标遗传方法 确定产生前列腺成纤维细胞，平滑肌细胞，血管周围细胞和尿液的祖细胞 肌肉括约肌肌细胞。我们将使用免疫染色和多光谱成像分配标记的谱系 细胞到前列腺基质子群的两二维图。这些数据将显示 使用创新的在线工具，该工具将研究人员与经过验证的表达CRE的鼠标线和基质联系起来 细胞选择性抗体。我们的第二个目的是创建发展的人类前列腺基质RNA和蛋白质 表达地图集以刺激与前列腺疾病相关的假设，从而导致基质的行为 AIM 1中确定的祖细胞。我们将绘制关键增长因素，接收器和 可能介导前列腺基质和上皮分化的转录因子。这项工作 完成了我们先前为GudMap制作的高分辨率开发小鼠前列腺图形。我们的结果 将用于生成前列腺开发的在线教程，我们将确定同源隔室 在老鼠和人之间。我们将在可能的情况下以与之前使用的相同术语进行注释 要注释鼠标数据，提供可搜索的在线数据集，该数据集使研究人员可以比较 小鼠与人之间的RNA/蛋白质表达，并识别跨物种的构成途径。我们的数据 将为前列腺研究社区提供设计和测试有关有关的新假设的必要工具 前列腺基质在良性增生，感染，疼痛和癌症中的致病作用。