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

Nat Genet. 2020 Sep;52(9):908-918. doi: 10.1038/s41588-020-0642-1. Epub 2020 Aug 17.

Abstract

The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion of Pten in Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Lineage / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / metabolism
  • Organoids / cytology
  • Organoids / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Prostate / cytology*
  • Prostate / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Regeneration / physiology
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcriptome / genetics*

Substances

  • PTEN Phosphohydrolase