Pd03-01 Single-Cell Transcriptional Profiles of Benign Prostatic Hyperplasia Reveal a Progenitor-Like Luminal Epithelial Cell State Within the Inflammatory Microenvironment

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD03)1 May 2024PD03-01 SINGLE-CELL TRANSCRIPTIONAL PROFILES OF BENIGN PROSTATIC HYPERPLASIA REVEAL A PROGENITOR-LIKE LUMINAL EPITHELIAL CELL STATE WITHIN THE INFLAMMATORY MICROENVIRONMENT Rei Unno, Jon Akutagawa, Hanging Song, Heiko Yang, Takahiro Yasui, Franklin Huang, and Thomas Chi Rei UnnoRei Unno , Jon AkutagawaJon Akutagawa , Hanging SongHanging Song , Heiko YangHeiko Yang , Takahiro YasuiTakahiro Yasui , Franklin HuangFranklin Huang , and Thomas ChiThomas Chi View All Author Informationhttps://doi.org/10.1097/01.JU.0001009388.01015.e5.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is characterized by excessive cell growth and inflammation, and it commonly affects aging men. To develop new medical treatments for BPH, it is essential to gain a deeper understanding of the underlying pathophysiology and specific cell types involved. We aimed to examine the individual cellular states in BPH at the single-cell level and identify cell populations that play a significant role in cell growth and inflammation. METHODS: We conducted single-cell RNA sequencing of prostate tissues from 15 patients who underwent holmium laser enucleation of the prostate for BPH treatment. We then used clustering and differential expression analyses to categorize all the cell types in the obtained single-cell RNA-seq data. Subsequently, we performed pseudo-time, gene set enrichment, gene ontology, and ligand-receptor analyses. RESULTS: We analyzed 16,234 cells and identified distinct subgroups within stromal, epithelial, and immune cell populations that were strongly linked to inflammation. Additionally, we identified a rare luminal subgroup characterized by elevated expression of macrophage migration inhibitory factor (MIF), KLK4, and HOXB13. Pseudo time analysis revealed that this luminal subgroup had closer ties to club and basal cells and might represent a potential precursor state for luminal cells. We observed a significantly higher stem cell signature score in the luminal subgroup, derived from epithelial stem cells, suggesting that this subgroup may be a key driver of prostate cell proliferation. We also explored ligand-receptor interactions between stromal, epithelial, and immune cells using CellPhoneDB. Thus, uncovering unique interactions between fibroblasts and the progenitor luminal subgroup involving MIF, a pro-inflammatory cytokine that stimulates epithelial cell growth and prostate inflammation. Moreover, this luminal subgroup interacts with neutrophils and macrophages via MIF. CONCLUSIONS: Our single-cell profiling of BPH provides a roadmap for inflammation-linked cell subgroups and highlights a novel luminal progenitor subgroup that interacts with other cell groups via MIF, which may contribute to the prostate cell inflammatory phenotype and proliferation associated with BPH. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e76 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Rei Unno More articles by this author Jon Akutagawa More articles by this author Hanging Song More articles by this author Heiko Yang More articles by this author Takahiro Yasui More articles by this author Franklin Huang More articles by this author Thomas Chi More articles by this author Expand All Advertisement PDF downloadLoading ...