Single-cell transcriptomics identifies a distinct luminal progenitor cell type in distal prostate invagination tips.

Area of Science:

• Urology
• Cell Biology
• Cancer Research

Background:

• Understanding prostate epithelial cell hierarchy is key to unraveling prostate cancer origins.
• Prostate stem/progenitor cell identification is crucial for cancer research.

Purpose of the Study:

• To identify and characterize prostate stem/progenitor cells.
• To elucidate the prostate epithelial cell lineage hierarchy.
• To investigate the cellular origins of prostate cancer.

Main Methods:

• Single-cell RNA sequencing of mouse and human prostate cells.
• In vitro organoid formation assays.
• In vivo prostate epithelial duct regeneration studies.
• Lineage tracing experiments.
• Pten deletion in specific cell populations.

Main Results:

• A unique luminal cell type (Luminal-C) was identified, marked by Tacstd2, Ck4, and Psca.
• Distal prostate Luminal-C cells (Dist-Luminal-C) demonstrated enhanced organoid formation and regenerative capacity.
• Lineage tracing confirmed Dist-Luminal-C cells as self-renewing progenitors of distal prostate luminal lineages.
• Pten deletion in Dist-Luminal-C cells induced prostatic intraepithelial neoplasia.
• Human prostate cells (h-Luminal-C) confirmed the existence of this cell type.

Conclusions:

• Dist-Luminal-C cells are identified as the luminal progenitor population in distal prostate invagination tips.
• This study provides critical insights into prostate lineage hierarchy.
• Distal Luminal-C cells represent a potential cellular origin for prostate cancer initiation.