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Updated: Dec 22, 2025
Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture
Published on: November 22, 2019
Regenerative potential of prostate luminal cells revealed by single-cell analysis
Wouter R Karthaus1, Matan Hofree2, Danielle Choi1
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Abstract:
Androgen deprivation is the cornerstone of prostate cancer treatment. It results in involution of the normal gland to ~90% of its original size because of the loss of luminal cells. The prostate regenerates when androgen is restored, a process postulated to involve stem cells. Using single-cell RNA sequencing, we identified a rare luminal population in the mouse prostate that expresses stemlike genes (Sca1 + and Psca +) and a large population of differentiated cells (Nkx3.1 +, Pbsn +). In organoids and in mice, both populations contribute equally to prostate regeneration, partly through androgen-driven expression of growth factors (Nrg2, Rspo3) by mesenchymal cells acting in a paracrine fashion on luminal cells. Analysis of human prostate tissue revealed similar differentiated and stemlike luminal subpopulations that likewise acquire enhanced regenerative potential after androgen ablation. We propose that prostate regeneration is driven by nearly all persisting luminal cells, not just by rare stem cells.
Insights
Prostate regeneration after androgen deprivation involves both stemlike and differentiated luminal cells, not just rare stem cells. This finding challenges the traditional view and offers new insights into prostate stem cell biology.
Area of Science:
- Urology
- Stem Cell Biology
- Prostate Cancer Research
Background:
- Androgen deprivation therapy is a primary treatment for prostate cancer, causing significant prostate gland involution.
- Prostate regeneration upon androgen restoration is believed to involve stem cells, but the exact mechanisms remain unclear.
Purpose of the Study:
- To investigate the cellular mechanisms driving prostate regeneration after androgen ablation.
- To identify specific cell populations responsible for prostate regrowth and their roles.
Main Methods:
- Single-cell RNA sequencing was employed to profile cell populations in mouse prostates.
- Organoid models and in vivo mouse studies were used to assess regenerative capacity.
- Analysis of human prostate tissue complemented mouse studies.
Main Results:
- A rare stemlike luminal cell population (Sca1+, Psca+) and a larger differentiated luminal cell population (Nkx3.1+, Pbsn+) were identified in mice.
- Both cell populations contributed equally to prostate regeneration.
- Mesenchymal cells release growth factors (Nrg2, Rspo3) that promote luminal cell regeneration in an androgen-dependent manner.
- Similar cell subpopulations with enhanced regenerative potential were observed in human prostate tissue.
Conclusions:
- Prostate regeneration is driven by a broader population of luminal cells, including differentiated cells, rather than exclusively by rare stem cells.
- This challenges the established paradigm of prostate stem cell-driven regeneration.
- Findings suggest a more inclusive model for prostate tissue repair and regeneration.
