Single-cell RNA-sequencing technology demonstrates the heterogeneity between aged prostate peripheral and...

Area of Science:

• Urology
• Cell Biology
• Genomics

Background:

• Cellular and functional heterogeneity in the aged prostate is crucial for understanding disease distribution.
• Distinct zones, the peripheral zone (PZ) and transitional zone (TZ), exhibit unique cellular characteristics.

Purpose of the Study:

• To identify and characterize cellular heterogeneity within aged human prostate peripheral zone (PZ) and transitional zone (TZ).
• To elucidate the functional differences and spatial distribution of cell types between the PZ and TZ.

Main Methods:

• Single-cell RNA-sequencing of aged human prostate PZ and TZ tissues.
• Validation of findings using immunofluorescence staining.

Main Results:

• Club/hillock epithelial cells in the TZ display high NOTCH signaling and stem-like properties, with lower androgen gene expression.
• A novel TFF3+ luminal subtype with elevated MYC/E2F activity was identified in the PZ.
• The TZ exhibits higher stem and inflammation pathway activity but lower androgen/lineage activity compared to the PZ.
• The TZ immune microenvironment is more complex, with increased NK and Treg cells, and fibroblasts show heightened activity in immunity and proliferation.

Conclusions:

• Significant heterogeneity exists between the aged prostate TZ and PZ, characterized by distinct cellular compositions and functional pathways.
• These findings provide insights into the spatial distribution of prostate diseases and potential targets for novel therapies.