Unveiling the Regenerative Capacity of Prostate Cells via Single-Cell Study
Summary
The utilization of androgen deprivation therapy for the treatment of prostate cancer is widely recognized as an effective approach. This intervention results in a reduction in the size of the prostate gland due to the loss of luminal cells. Nonetheless, the restoration of androgen levels has been demonstrated to result in the regeneration of the prostate gland, a process believed to be reliant on stem cells. Recent studies employing single-cell RNA sequencing in animal models have revealed the presence of a population of luminal cells with stem cell characteristics, as well as a larger population of differentiated cells. Both cell populations contribute to prostate regeneration through the regulation of growth factor expression by mesenchymal cells in response to androgen. Similar observations have been made in human prostate tissue, indicating that the regenerative capacity of the prostate gland is not solely dependent on stem cells, but also on nearly all persisting luminal cell populations. These findings may have implications for future research endeavors aimed at enhancing prostate regeneration therapy.
Fig.1 Model of prostate regeneration. (Karthaus, 2022)
Research Criteria
When a man has surgery or takes medicine to lower their hormone levels, their prostate gets smaller by about 90%. This happens because some cells in the prostate are lost. But when doctors add back hormones, the prostate can grow back completely in just 4 weeks. Scientists want to understand how this happens and are using a special test called scRNA-seq to study cells in both mice and humans. They want to see how these cells change during the shrinking and growing of the prostate.
Sample Type
Prostate tissues from humans and mice.
Result—Cell Clusters of the Intact Prostate
The researchers collected 13,398 cells from the mouse prostate without the use of fluorescence-activated cell sorting in order to undertake droplet-based single-cell RNA sequencing (scRNA-seq) in order to understand the cellular makeup of the prostate (FACS). They discovered 15 distinct cell subgroups using unsupervised graph clustering, which were further subdivided into 22 subsets, comprising 6 epithelial and 16 non-epithelial subsets. The researchers additionally examined Epcam-positive and -negative cells obtained using FACS to ensure the complete representation of all epithelial cells. The outcomes, however, showed a marked deterioration in quality and a nearly complete extinction of two luminal groups.
Fig.2 Luminal cells identified by scRNA-seq of the intact mouse prostate. (Karthaus, 2022)
Result—Gene Expression Changes in the Mouse Prostate Across a Castration/Regeneration Cycle
By gathering scRNA-seq profiles throughout the full castration/regeneration (C/R) cycle, a systematic examination of the mouse prostate was carried out. Using cell surface markers that differentiate between the two cell populations, FACS was used to compare the relative representation of L1 and L2 cells in castrated mice. According to scatterplots of L1 versus L2 signature scores from the computational analysis of transcriptomes across the C/R cycle, L1 cells underwent a significant change to resemble L2 cells after castration (at day 28), but this change was reversed during the regeneration phase. The outcomes also showed that the transcriptional profiles of L1 and L2 cells were tightly integrated on day 28 following regeneration, as seen in the images.
Fig.3 Transcriptomic changes in murine luminal subpopulations during castration and organ regeneration. (Karthaus, 2022)
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Reference
- Karthaus, W.R.; et al. Regenerative potential of prostate luminal cells revealed by single-cell analysis. Science, 2022, 368(6490): 497-505.
