A single cell transcriptional profile of benign prostatic hyperplasia

TL;DR

This study uses single-cell RNA sequencing to analyze prostate tissue from men with benign prostatic hyperplasia, identifying cell subgroups linked to inflammation and a potential precursor cell type.

Contribution

The study identifies a rare luminal cell subgroup with a stem cell-like signature and its interactions with immune and stromal cells via MIF in BPH.

Findings

A rare luminal subgroup with a high stem cell signature was identified in BPH tissue.

Ligand-receptor interactions involving MIF were found between the luminal subgroup and fibroblasts/macrophages.

The luminal subgroup is suggested to be a progenitor state contributing to BPH inflammation and proliferation.

Abstract

Benign prostatic hyperplasia (BPH) is characterized by excessive cell proliferation and inflammation and affects most aging men. The development of new therapies for BPH requires a deeper understanding of the underlying pathophysiology and cellular components of BPH. Single-cell RNA-sequencing was performed on prostate tissue from 15 patients undergoing holmium laser enucleation of the prostate for treatment of BPH. Clustering and differential expression analysis on aligned single-cell RNA-seq data was performed to annotate all cell types. 16,234 cells were analyzed and specific stromal, epithelial, and immune subgroups were found to be strongly associated with inflammation. A rare luminal subgroup was identified and pseudotime analysis indicated this luminal subgroup might give rise to other luminal cells. Using a gene set derived from epithelial stem cells, we found that this luminal subgroup had a significantly higher stem cell signature score than all other epithelial subgroups, suggesting this subgroup is a luminal precursor state. Ligand-receptor interactions between stromal, epithelial, and immune cells were explored with CellPhoneDB. Significant interactions involving MIF, a pro-inflammatory cytokine that promotes epithelial cell growth and inflammatory response in the prostate, were identified between the progenitor-like luminal subgroup and both fibroblasts and macrophages. Our single-cell profiling of BPH provides a roadmap for investigating inflammation-linked cell subgroups and highlights a progenitor-like luminal subgroup interacting with other cell groups via MIF that may contribute to the inflammation and cell proliferation phenotype associated with BPH.

The online version contains supplementary material available at 10.1038/s41598-025-02417-w.

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