Scientists have discovered a distinct subtype of cell in the prostate and it could help solve the mystery of why the gland increases in size with age. This natural phenomenon is called benign prostatic hyperplasia (BPH) and tends to occur in a single region of the prostate. But scientists still don’t understand why. Now, researchers at Johns Hopkins University have found a possible culprit hiding around the urethra. Using single-cell RNA sequencing, the team has identified a population of prostate cells that are particularly abundant. in this region, especially in cases of BPH. The findings are published in The Journal of Pathology. “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,” explains lead author Vasan Yegnasubramanian. The transition zone is the part of the prostate that surrounds the urethra. If this area enlarges with age, it may restrict passage, making urination slower and more sporadic. It is the most common prostate problem in men over 50, and although changes in hormone levels, inflammation and cell growth probably play a role, no one really knows why, at a cellular level, BPH occurs. Benign prostatic hyperplasia, 3D illustration showing a normal and enlarged prostate. (KATERYNA KON/Science Photo Library RF/Getty Images) Urologist Charles Welliver of Albany Medical College was not involved in the recent study, but in an interview for the Urology Care Foundation podcast in August, he explained that BPH is not due to swelling. “Benign prostatic hyperplasia is simply an increase in the number of cells within the prostate,” Welliver said. “So the cells do not grow, but rather increase in number.” Now, scientists believe they have discovered what units could be behind that cellular increase. Johns Hopkins researchers analyzed noncancerous prostate tissue from 10 men who had prostate cancer. The samples came from the three main areas of the prostate, and the researchers carefully analyzed which genes were turned on or off in almost 130,000 individual cells. In tissues from the transition zone and in BPH samples, the researchers found a distinct cell population that was rare in other parts of the prostate. These cells are a subtype of basal cells called WIF1+, and are transcriptionally and anatomically distinct from the rest of their family members. Scientists say they show a unique gene expression profile, and RNA sequencing and staining show they are markedly enriched in the transition zone of the human prostate. Some genes associated with WIF1+ cells respond to androgens such as testosterone and are involved in signaling pathways that influence prostate growth and development. “Together,” the authors write, “the molecular signature, zonal distribution, and pathway enrichment suggest that WIF1+ basal cells enriched in the transition zone may contribute to the pathogenesis of BPH by promoting epithelial and stromal remodeling.” The researchers also speculate that by dampening inflammation and a growth signaling pathway called WNT, these cells could help explain why prostate cancer begins less frequently in the transition zone. transition zone,” says first author Rulin Wang. When Wang and his colleagues analyzed publicly available data sets, they found more evidence to support their results. Enlarged prostate gland tissues were enriched with WIF1+ basal cells. The genetic signature of these abundant basal cells was also clearly altered. Wang says this raises the possibility that these cells “contribute to regional processes that make the transition zone particularly susceptible to BPH.” and colleagues believe it deserves further investigation. Future studies, for example, could examine the functional roles of WIF1+ basal cells in the development of prostate enlargement. If these cells indeed play a direct role in BPH, they could become future drug targets. The research has been published in The Journal of Pathology. This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. While we take pride in our process, we are human. If you spot an error, please let us know.
