MP06-01 IDENTIFICATION OF COGNATE PROXIMAL CELL TYPES OF THE MOUSE AND HUMAN PROSTATE AND THEIR ENRICHMENT IN HUMAN BENIGN PROSTATIC HYPERPLASIA

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (MP06)1 Apr 2020MP06-01 IDENTIFICATION OF COGNATE PROXIMAL CELL TYPES OF THE MOUSE AND HUMAN PROSTATE AND THEIR ENRICHMENT IN HUMAN BENIGN PROSTATIC HYPERPLASIA Diya Binoy Joseph, Gervaise Henry, Alicia Malewska, Kyle Wegner, Jeffrey Reese, Ryan Mauck, Jeffrey Gahan, Ryan Hutchinson, Claus Roehrborn, Chad Vezina, and Douglas Strand* Diya Binoy JosephDiya Binoy Joseph More articles by this author , Gervaise HenryGervaise Henry More articles by this author , Alicia MalewskaAlicia Malewska More articles by this author , Kyle WegnerKyle Wegner More articles by this author , Jeffrey ReeseJeffrey Reese More articles by this author , Ryan MauckRyan Mauck More articles by this author , Jeffrey GahanJeffrey Gahan More articles by this author , Ryan HutchinsonRyan Hutchinson More articles by this author , Claus RoehrbornClaus Roehrborn More articles by this author , Chad VezinaChad Vezina More articles by this author , and Douglas Strand*Douglas Strand* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000820.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is highly prevalent in aging men and poses a significant healthcare burden associated with the treatment of Lower Urinary Tract Symptoms (LUTS). BPH/LUTS remain difficult to treat because of phenotypic heterogeneity, resulting in the need for surgical intervention. The cell types that originate BPH growth are not known. Anatomical studies have shown that the transition zone located near the urethra is the site of BPH growth. We previously identified two novel cell types, club and hillock, that are enriched in the prostatic urethra and proximal ducts. Here, we identify a new proximal fibroblast in the human as well as cognate hillock epithelia and proximal fibroblasts in the mouse. We assess the contribution of each proximal cell type in human BPH, establishing a new paradigm for urethral epithelia and proximal fibroblasts in discrete BPH phenotypes. METHODS: We used an unbiased approach by single cell RNA-sequencing (scRNA-seq) to identify cognate cell types of the mouse and human prostate and develop new flow cytometry and IHC antibody panels to purify and locate each cell type. The frequency of proximal fibroblasts and urethral epithelia in BPH vs. normal human prostate was assessed using scRNA-seq, flow cytometry, and immunofluorescence. RESULTS: Hillock and club cell identity is established early and these cells extend into the proximal ducts of the adult prostate transition zone. Proximal fibroblasts surround the urethra and proximal ducts. BPH patients have increased club and hillock cells within glandular nodules compared to normal prostate tissue and proximal fibroblasts are increased in areas of peri-urethral fibrosis. Mouse scRNA-seq and IHC data confirmed the existence of cognate proximal fibroblasts and hillock epithelia, but club cells were not found. CONCLUSIONS: Our results show that club and hillock epithelia of the urethra and proximal ducts are established before prostate budding and are enriched in BPH glandular nodules, suggesting a potential cellular origin for new prostate growth. We also identify the proximal fibroblast of the human as the cellular source of collagen deposition in prostatic fibrosis, setting up a new phenotype to target in patients with LUTS. We created a cellular atlas of the mouse urethra and proximal prostate, which will allow for the generation of specialized mouse models to trace urethral and proximal fibroblast lineages. The cell types of the proximal ducts could become novel targets for the treatment of BPH/LUTS. Source of Funding: R01 DK115477 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e51-e51 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diya Binoy Joseph More articles by this author Gervaise Henry More articles by this author Alicia Malewska More articles by this author Kyle Wegner More articles by this author Jeffrey Reese More articles by this author Ryan Mauck More articles by this author Jeffrey Gahan More articles by this author Ryan Hutchinson More articles by this author Claus Roehrborn More articles by this author Chad Vezina More articles by this author Douglas Strand* More articles by this author Expand All Advertisement PDF downloadLoading ...