Researchers at Johns Hopkins University have identified a previously unrecognised population of cells concentrated around the urethra that could help explain why the prostate commonly enlarges with age, a condition known as benign prostatic hyperplasia (BPH).
Single-cell analysis points to a local cellular source
Using single-cell RNA sequencing, the team analysed non-cancerous prostate tissue from 10 men undergoing prostate cancer surgery and profiled gene activity in nearly 130,000 individual cells. The work, published in The Journal of Pathology, revealed a distinct subtype of prostate cell that is particularly abundant in the region that surrounds the urethra — the prostate’s transition zone — and more frequent in instances of BPH.
The localization of this cell population dovetails with a long-standing clinical mystery: BPH tends to develop in the transition zone while other prostate regions remain relatively spared. When that zone enlarges it can compress the urethra, producing the slow, sometimes intermittent urination that characterises the condition.
“Although BPH affects millions of men worldwide, scientists still do not fully understand why it develops primarily in a region of the prostate known as the transition zone, while other regions of the gland remain relatively unaffected,” said senior author Vasan Yegnasubramanian.
Why the finding matters
Urologists and researchers have long pointed to hormones, inflammation and cell proliferation as contributors to BPH, but none of those explanations fully account for the anatomical specificity. Identifying a cell type concentrated where BPH develops offers a concrete cellular target to test mechanisms and, potentially, therapies.
- Study size and method: tissue from 10 men; ~130,000 cells profiled with single-cell RNA sequencing.
- Finding: a distinct cell population enriched in the prostate transition zone and associated with BPH samples.
- Implication: a localised cell population may underlie the regional development of BPH and guide future treatments.
Context, caveats and next steps
Experts not involved in the study stress that BPH is a complex condition. In a separate commentary, urologist Charles Welliver described BPH fundamentally as an increase in cell number rather than cell size — a point consistent with a discovery focused on a particular proliferative cell population. But he and others caution that linking a cell type to disease causation requires additional evidence, including functional studies and confirmation in larger, more diverse cohorts.
The current dataset derives from men who had prostate cancer, though the sampled tissue was non-cancerous. That raises questions about whether the observed cell population reflects typical ageing processes in men without cancer. The researchers will need to replicate findings in independent cohorts and to perform mechanistic experiments — for instance, tracing how those cells respond to inflammatory signals, hormonal changes or ageing-related molecular pathways.
| Feature | Value |
|---|---|
| Donor samples | 10 men (non-cancerous tissue) |
| Cells profiled | ~130,000 individual cells |
| Publication | The Journal of Pathology |
If future research supports a causal role for this cell subtype in driving prostate enlargement, it could open new avenues for targeted therapy. Current medical treatments for BPH include medications that alter hormone signalling or relax smooth muscle, and surgical interventions for severe obstruction. A therapy directed at a specific cell population or its signalling pathways might reduce symptoms with fewer systemic effects.
For clinicians and patients, the discovery offers a clearer anatomical and cellular hypothesis to test. For science and medicine, it highlights the power of single-cell technologies to reveal cell types and states that bulk tissue analyses miss. But as with many early-stage discoveries, translation from cell atlas to clinical care will require substantial follow-up.
The study advances our understanding of why certain parts of the prostate are vulnerable to age-related growth and sets a research agenda: validate the finding in broader populations, determine the cell population’s biological role, and explore whether modulating it can prevent or reverse problematic prostate enlargement.
