A transition zone enriched WIF1⁺ basal cell subtype is associated with benign prostatic hyperplasia
Wang, R.; Zheng, Q.; Graham, M. K.; Vaghasia, A.; Liu, J.; Gregg, J.; Jones, T.; Gupta, A.; Castagna, N.; Zhang, Y.; Schuebel, K.; Meyers, J.; Skaist, A.; Hoyle, D.; Yang, Y.; Nelson, W. G.; De Marzo, A. M.; Yegnasubramanian, S.
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ABSTRACT/SUMMARYThe cellular composition and disease susceptibilities of the distinct zones of the human prostate remain incompletely understood. Through extensive single-cell RNA sequencing (scRNA-seq) of benign regions from prostatectomy specimens, we identified a basal cell population expressing WIF1, VCAN, and NRG1, among other genes, that was significantly enriched in the transition zone (TZ). Benign prostatic hyperplasia (BPH) is a common condition that causes widespread morbidity and is nearly exclusively localized to the TZ. Analysis of previously published scRNA-seq datasets further confirmed that WIF1+ basal cells were significantly enriched in BPH compared to normal prostate. Pathway and cell-cell communication analyses revealed that this basal subtype is associated with programs related to cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, and hormone response. Together, the molecular signature, zonal distribution, and pathway enrichment suggest that TZ-enriched WIF1+ basal cells may contribute to BPH pathogenesis by promoting epithelial and stromal remodeling.
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