Molecular and fate maps of prostatic stroma

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， 前列腺基质，即使它驱动大多数前列腺的重要生物学行为。前列腺基质 启动腺体发育，并释放旁分泌信号，刺激上皮生长， 增生和癌症。它还合成介导再生修复的细胞外基质分子， 增加器官僵硬，最近与泌尿功能障碍有关的因素。前列腺间质定位 祖细胞和参与其增殖和分化的因子是鉴定细胞增殖和分化的第一步。 负责基于基质的疾病过程的机制。我们的第一个目标是使用小鼠遗传方法， 鉴定产生前列腺成纤维细胞、平滑肌细胞、血管周围细胞和尿纹状细胞的祖细胞 括约肌肌细胞我们将使用免疫染色和多光谱成像来分配标记的谱系 细胞的二维和三维地图的前列腺基质亚室。这些数据将在 使用一种创新的在线工具，将研究人员与经过验证的表达cre的小鼠品系和基质连接起来， 细胞选择性抗体我们的第二个目标是建立一个发展中的人类前列腺基质RNA和蛋白质 表达图谱，以刺激与前列腺疾病相关的假设， 目的1中鉴定的祖细胞。我们将绘制关键生长因子、受体和 这些转录因子可能介导前列腺基质和上皮分化。这项工作 补充了我们之前为GUDMAP制作的高分辨率显影小鼠前列腺图谱。我们的结果 将用于生成前列腺发育的在线教程， 老鼠和人类之间的区别我们将在可能的情况下使用之前使用的相同术语注释人类数据 注释小鼠数据，提供可搜索的在线数据集，使研究人员能够比较 小鼠和人类之间的RNA/蛋白质表达，并确定跨物种的保守途径。我们的数据 将为前列腺研究界提供必要的工具，以设计和测试新的假设， 前列腺间质在良性增生、炎症、疼痛和癌症中的致病作用。

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.