biostudies-literatureYan QBeijing Hospital Clinical Research 121 ProjectInnovation project of Peking Union Medical CollegeDiscipline Construction Project of Peking Union Medical CollegeBeijing Municipal Science and Technology ProjectNational Natural Science Foundation of Chinae1084https://www.ebi.ac.uk/biostudies/studies/S-EPMC9574492biostudies-literatureUnknown12(10)<h4>Background</h4>Identifying cellular and functional heterogeneity within aged prostate is critical for understanding the spatial distribution of prostate diseases.<h4>Methods</h4>Aged human prostate peripheral zone (PZ) and transitional zone (TZ) tissues were used for single-cell RNA-sequencing. Results were validated by immunofluorescence staining.<h4>Results</h4>We found that club/hillock epithelial cells, compared with other epithelial cells, had significantly higher NOTCH signaling activity and expressed higher levels of neuro-stems but lower androgen-related genes. These cells were primarily found in the TZ and provided a stem-like niche around the proximal prostate ducts. Significant heterogeneity was observed in the aged luminal population. A novel TFF3+ luminal subtype with elevClinical and translational medicineSingle-cell RNA-sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone.PMC9574492201920202101BJ-2018-0902019-1002-6981900700Z20110000562000782202900Wang MXia HYan QDai CLong XLiu MZhang HDiao TWang YHou HfalseSingle-cell RNA-sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone.<h4>Background</h4>Identifying cellular and functional heterogeneity within aged prostate is critical for understanding the spatial distribution of prostate diseases.<h4>Methods</h4>Aged human prostate peripheral zone (PZ) and transitional zone (TZ) tissues were used for single-cell RNA-sequencing. Results were validated by immunofluorescence staining.<h4>Results</h4>We found that club/hillock epithelial cells, compared with other epithelial cells, had significantly higher NOTCH signaling activity and expressed higher levels of neuro-stems but lower androgen-related genes. These cells were primarily found in the TZ and provided a stem-like niche around the proximal prostate ducts. Significant heterogeneity was observed in the aged luminal population. A novel TFF3+ luminal subtype with elev2022-01-01T00:00:00Z2022 Oct2025-04-27T03:35:17.501Z2025-04-06T18:55:12.99ZS-EPMC95744923624532410.1002/ctm2.1084