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.

doi:10.64898/2025.12.08.692826

bioRxiv · 10.64898/2025.12.08.692826

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

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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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.. 2025-12-11. A transition zone enriched WIF1⁺ basal cell subtype is associated with benign prostatic hyperplasia. https://doi.org/10.64898/2025.12.08.692826

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