New prostate cell type may explain age-related enlargement

Johns Hopkins researchers identify WIF1+ basal cells as a potential cellular driver of benign prostatic hyperplasia.

By LineZotpaper AI staff

Published25 October 2026

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Illustration: New prostate cell type may explain age-related enlargement

Researchers at Johns Hopkins University have identified a distinct subtype of prostate cell that accumulates in the gland's transition zone, offering a new hypothesis for why benign prostatic hyperplasia (BPH) develops with age. The findings, published in The Journal of Pathology, point to WIF1+ basal cells as a potential trigger for the condition that affects millions of men over 50.

The prostate's transition zone, which surrounds the urethra, is the primary site for BPH. As it enlarges, it constricts the urethra, causing the slower, sporadic urination common in older men. Until now, scientists attributed the condition to hormone changes, inflammation, and cell growth, but a specific cellular trigger has remained elusive.

To investigate, the team led by senior author Vasan Yegnasubramanian analysed noncancerous prostate tissue from ten men. Using single-cell RNA sequencing, they examined nearly 130,000 individual cells across the prostate's three major zones. In the transition zone and in BPH tissue, they found a population of cells rare elsewhere: a subtype of basal cell they have named WIF1+.

"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," Yegnasubramanian said.

The WIF1+ cells are transcriptionally and anatomically distinct, with a unique gene expression profile. Some of their genes respond to androgens like testosterone and are involved in signalling pathways that influence prostate growth. "Together, the molecular signature, zonal distribution, and pathway enrichment suggest that transition-zone-enriched WIF1+ basal cells may contribute to BPH pathogenesis by promoting epithelial and stromal remodeling," the authors write in The Journal of Pathology.

First author Rulin Wang noted that analysis of publicly available datasets further supported the findings, showing that enlarged prostate tissues were enriched with these cells. "This raises the possibility that these cells contribute to the regional processes that make the transition zone particularly susceptible to BPH," Wang said.

The source confirms that BPH represents an increase in cell number rather than swelling, a distinction highlighted by urologist Charles Welliver of Albany Medical College in an interview for the Urology Care Foundation's podcast. The researchers also speculate that by dampening inflammation and the WNT signalling pathway, WIF1+ cells might help explain why prostate cancer develops less frequently in the transition zone.

The team emphasises that the findings are a hypothesis requiring further investigation. If a direct role in BPH is confirmed, these cells could become targets for new drug therapies.

Analysis

Why This Matters

BPH is the most common prostate problem in men over 50, affecting quality of life and urinary function for millions.
The discovery offers a specific cellular mechanism for a condition whose origins have long puzzled scientists.
If confirmed, WIF1+ cells could serve as a direct target for new drug therapies designed to prevent or reverse enlargement at its source.

Background

Benign prostatic hyperplasia (BPH) has been recognised as a common consequence of ageing, particularly in the transition zone of the prostate surrounding the urethra. While hormonal changes, notably in androgens, and general inflammation have been linked to the condition, the exact cell-level trigger has remained unidentified. Research published in The Journal of Pathology by a Johns Hopkins University team now proposes that a specific and previously unknown subtype of basal cell may be the key.

Key Perspectives

Johns Hopkins University researchers: The team argues that WIF1+ basal cells are transcriptionally distinct and enriched in the transition zone, particularly in BPH cases, hypothesising that they promote epithelial and stromal remodeling that leads to enlargement and may also suppress inflammation and cancer growth in that region. First author Rulin Wang cautioned that the work raises a "possibility" that requires further investigation.

Charles Welliver (Albany Medical College): Speaking on the Urology Care Foundation's podcast, Welliver provided an important distinction regarding the nature of BPH, clarifying that it represents an increase in the number of cells within the prostate rather than an enlargement of individual cells.

What to Watch

Future studies will need to establish the direct functional role of WIF1+ cells in prostate growth and BPH progression.
If a causative link is confirmed, the unique molecular profile of these cells could make them attractive targets for drug development.
Replication of the findings in larger and more diverse tissue samples will be critical for validating the hypothesis.

Sources

Scientists May Have Discovered Why Men's Prostates Enlarge With Age · ScienceAlert

Checked

12 claims in this story checked against 1 source: 9 supported.

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SupportedA new prostate cell type may explain age-related enlargement.ScienceAlert: “Scientists May Have Discovered Why Men's Prostates Enlarge With Age. Scientists have discovered a distinct subtype of cell in the prostate, and it could help solve the mystery of why the gland enlarges with age.”
SupportedWIF1+ basal cells are a potential cellular driver of BPH.ScienceAlert: “These cells are a subtype of basal cells called WIF1+”
Partly supportedThe condition affects millions of men over 50.ScienceAlert: “Although BPH affects millions of men worldwide”
SupportedYegnasubramanian said: “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.”ScienceAlert: ““Although BPH affects millions of men worldwide, scientists still do not 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,” explains senior author Vasan Yegnasubramanian.”
Partly supportedThe team led by senior author Vasan Yegnasubramanian analysed noncancerous prostate tissue from ten men.ScienceAlert: “Researchers at Johns Hopkins analyzed noncancerous prostate tissue from 10 men who had prostate cancer.”
SupportedThe researchers examined nearly 130,000 individual cells across the prostate’s three major zones.ScienceAlert: “Samples came from the three major zones of the prostate, and researchers carefully analyzed which genes were turned on or off in nearly 130,000 individual cells.”
SupportedWIF1+ cells were found in the transition zone and BPH samples, and were rare elsewhere.ScienceAlert: “In tissues from the transition zone and in samples from BPH, researchers found a distinct cell population that was rare in other parts of the prostate.”
Partly supportedScientists had attributed BPH to hormone changes, inflammation and cell growth.ScienceAlert: “while changes to hormone levels, inflammation, and cellular growth probably play a role, no one really knows why, at a cellular level, BPH occurs.”
SupportedThe authors wrote that the cells’ signature, distribution and pathway enrichment suggest they may contribute to BPH by promoting epithelial and stromal remodeling.ScienceAlert: ““Together,” the authors write, “the molecular signature, zonal distribution, and pathway enrichment suggest that transition-zone-enriched WIF1+ basal cells may contribute to BPH pathogenesis by promoting epithelial and stromal remodeling.””
SupportedSome WIF1+ cell genes respond to androgens such as testosterone and are involved in pathways that influence prostate growth.ScienceAlert: “Some genes associated with WIF1+ cells respond to androgens like testosterone and are involved in signaling pathways that influence prostate growth and development.”
SupportedUrologist Charles Welliver of Albany Medical College said BPH is an increase in cell number rather than swelling in a Urology Care Foundation podcast interview.ScienceAlert: “Urologist Charles Welliver at Albany Medical College was not involved in the recent study, but in an interview for the Urology Care Foundation's podcast in August, he explained that BPH isn't due to swelling. “Benign prostatic hyperplasia is just an increase in the number of cells within the prostate,” said Welliver.”
SupportedResearchers speculate that dampening inflammation and WNT signalling could help explain why prostate cancer starts less often in the transition zone.ScienceAlert: “The researchers also speculate that by dampening inflammation and a growth-signaling pathway called WNT, these cells could help explain why prostate cancer starts less often in the transition zone.”