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Molecular and fate maps of prostatic stroma

前列腺基质的分子和命运图谱

基本信息

批准号：
9492866
负责人：
CHAD M. VEZINA
金额：
$ 6.57万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
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/9492866
关键词：
Alpha Cell 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 Dimensions Disease Drug Targeting Duct (organ) structure Ductal Epithelial Epithelial Cells Epithelium Extracellular Matrix Fibroblasts Foundations Functional disorder Gene Expression Generations Genetic Genetic Transcription Goals Growth Growth Factor 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 Pain Paracrine Communication Pathogenesis Pathogenicity Pathway interactions Pattern Pericytes Pharmacology Population Positioning Attribute Principal Investigator Process Proliferating Prostate Prostatic 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 cell behavior cell type daughter cell design experience fetal genetic approach genetic manipulation human data innovation interest male online tutorial progenitor programs protein expression regenerative repaired resistance factors spectrograph stromal progenitor time use tool transcription factor urinary

项目摘要

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.

项目总结