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Investigating Changes in Paracrine Signaling and Basal Cell Plasticity During Prostatitis and Prostate Cancer Progression
- Bleeker, Joosje
- Advisor(s): Wang, Zhu A
Abstract
Prostate inflammation is associated with prostate cancer (PCa) development. Basal-to-luminal cell differentiation, a process partly regulated by canonical Wnt signaling, plays a crucial role in PCa initiation. Here, using a basal cell lineage tracing mouse model, I investigated how loss of Wnt/β-catenin signaling in basal cells affects basal-to-luminal differentiation during E. coli-induced prostatitis. Results revealed that β-catenin-null basal cells still gave rise to luminal cells, albeit with reduced capacity compared to wild-type cells. Further exploration using single-cell RNA sequencing (scRNA-seq) could unveil distinct subpopulations arising from these basal cells during prostatitis. Future studies should also aim to minimize inflammation variation in bacterial prostatitis models.Additionally, I examined how knockout of androgen receptor (AR) in stromal cells affected stromal-to-epithelial signaling. Bulk RNA sequencing of WT and AR-KO stromal cells and differential gene expression analysis identified potential gene candidates for future investigations into the impact of stromal AR deletion on PCa progression. This study provides insights into the intricate cellular and molecular processes underlying PCa initiation and development, shedding light on potential therapeutic targets.
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